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Transcript
Thank you, Niklas. Yeah, I thought what we would discuss is a scenario that we’re all kind of familiar with, right? There’s a patient, almost regardless of symptomatology, who comes to your office, maybe through the ER, who has a brain MRI that clearly is from a CSF leak, right? It’s clearly SIH. The Beck score is like nine out of nine. You know that there must be a leak, and we do a spine MRI, it’s normal. MR myelogram is normal. We do a CT myelogram, it’s normal. Dynamic CT myelogram is normal. Digital subtraction myelogram is normal. Everything is normal. But we know that this patient is low in spinal fluid.
What are some of the reasons that this could be the case, and what are some of the things that we could at least consider that’s going on? This is from maybe 10–15 years ago. We looked at 200–300 patients who had somewhat of a similar scenario—an abnormal brain MRI regardless of symptoms. And we looked at how many of those patients had a CSF leak at the level of the spine and how many of them had a CSF leak at the level of the skull base. Certainly, before that time, a lot of patients who had a brain MRI clearly from SIH were worked up to millions of dollars to look for a CSF leak at the level of the skull base, usually by looking for CSF rhinorrhea. They would get nuclear scans, contrast cisternograms, and we found that none of those patients actually had a CSF leak at the level of the spine. And so we would go to conference and say, oh, you know, that never ever happens. But there’s always an exception, of course. Yeah. That happens sometimes.
A lot of patients with headaches get some nasal congestion and they start just leaking snot out of their nose, and people think that that’s spinal fluid. And then a few years ago, we saw this young gentleman—well, he wasn’t really a gentleman, he called my nurse practitioner a really bad word—but he had really bad brain sagging, and I read a lot of scans on him, and he actually was found to have a skull base CSF leak, not CSF rhinorrhea, but it was leaking through the posterior fossa into the soft tissues of the neck. Our thinking was that it’s probably just kind of like bulk flow of CSF, right? It just gets pulled out of the spinal canal, and that’s why he has brain sagging and positional headaches. For a couple of years we said, well, you can get it from a skull base leak, but not with CSF rhinorrhea. But then, of course, there’s one patient who does happen to have that.
This is a young girl we treated I think about a year ago. She’d had two bouts of bacterial meningitis. She had CSF rhinorrhea. They worked her up elsewhere, and she had a lot of CSF in her oropharynx, in her soft palate, soft tissues of the neck. We did a DSM, a digital subtraction myelogram, lateral projection, and there you see that she’s leaking also from the posterior fossa into the oropharynx, and if they had only kept filming a few more seconds, you could see little drops coming out of her nose. So you can also get it with CSF rhinorrhea, but not from an anterior cranial fossa type of leak. This also is from the posterior fossa.
You could look into that. Maybe this is one of these exceptional patients who has a leak at the level of the skull base, and certainly that has been found in many, well maybe not many, but several other centers as well. This is a little bit similar to what we were talking about this morning—changes in compliance, or I sometimes like to call it pooling of CSF in patients who maybe don’t have a leak, but they have multiple cysts or they have this dural ectasia.
This is an example of that. This is an anesthesiologist who actually works at Cedars. That’s her MRI, right? Clearly, she must have a leak. She had an MR myelogram. She had several cysts. We did six DSMs on her that were all normal. We sent her for a photon counting CT that was totally normal. We did blood patches, glue injections. Temporary benefit but not cured. Then you could think, well, maybe she’s leaking from some of those cysts, we just can’t find it. Maybe she has a CSF-venous fistula we just can’t find it, or there’s just some pooling of CSF. Maybe that’s why she has this type of MRI scan, but these cysts are not that impressive. So I don’t think that that’s the case with her, but maybe with a patient like this.
This is somebody—you can see the kidneys on the side—that’s autosomal dominant polycystic kidney disease. You can see that pretty much on every level of her spine she has more or less irregular or regular diverticula, but no leak as far as we can tell. And maybe she’s just pooling CSF in those, so that’s another possibility. Or it can be this, what we call dural ectasia. You can see that in Marfan syndrome or Loeys-Dietz syndrome, a couple of other syndromes. You can also see it with ankylosing spondylitis, and they just have this giant sac of CSF, usually at the bottom of the spine, but not always. You can see it anywhere in the spine.
And it’s not just with these obvious connective tissue disorders. We’ve also seen it in people who are of exceptionally tall stature. The one that you can see on the left there—that was actually leaking a little bit from that dural ectasia. But by the time we saw him, he was not leaking anymore on our scans, but he still had identical symptoms, and we just treated him for his dural ectasia. So that’s something you can look into as well, but I won’t talk about it too much because Dr. Stoodley is going to talk about it after this presentation.
And then we’ve recently looked at patients that we have seen over the last four, five, six years or so who have these very tiny little extradural lateral CSF collections. We haven’t published that yet—we’ve submitted that. And basically it’s a situation like this. You can see on that digital subtraction myelogram on the right side, this is the nerve root or the nerve root sleeve. And then right underneath it, there’s a little bit of CSF. There’s a little bubble there. Most people would say that’s just a little diverticulum or maybe an accessory nerve root, but that’s not always the case. We looked at 31 patients who had that, where we found that on their DSM in the lateral decubitus position, and we offered surgery to 27 of them. 27 underwent surgery, and it was just exploratory surgery—what’s going on there—and we actually found a CSF leak in all 27 of those patients.
It can be a different type of situation, so these are just different examples of that. They all kind of look similar. They’re like these little collections of CSF. It looks pretty innocuous, right? There’s no vein coming out of it, there’s no extradural CSF collection, and it’s difficult to see just based on this digital subtraction myelogram if we’re dealing with this. So these are some examples of those patients who have a CSF-venous fistula. This is what that looks like on the digital myelogram: you see a little diverticulum, and then there’s a big vein attached to it. These are just different examples of that.
Most of those patients have CSF-venous fistula, but other patients have what Dr. Carlton Jones talked about earlier today—this little tear at the level of the pedicle. But there’s no SLEC, there’s no extensive extradural CSF collection associated with that. We tested a number of neuroradiologists if, just based on this DSM, they could differentiate the particular type of lateral leak from a CSF-venous fistula. And there was not a really good way of differentiating those, at least not based on the digital subtraction myelogram. So that’s something that you could look into as well, and I know that some of you at least have also found that, at least on myelography.
We talked earlier today about this azygos vein stenosis, something we also stumbled onto. These are patients with really bad brain sagging and all the symptoms of behavioral variant frontotemporal dementia. That’s really – you know I think Dr. Kranz calls it a really heartbreaking condition. It is, right, because usually these are young people. They’re middle-aged and they totally have lost their way of life. They cannot function in society. They sleep 20 hours a day. They are disinhibited. They make very suggestive remarks. They make jokes at funerals. They exhibit apathy. They’ll brush their teeth for two, three hours until you tell them to stop brushing their teeth.
And it’s really a genetic disease, right? I actually know identical twins. One of them has that, the other one does not have that. So it can be an acquired genetic problem, right? It’s not necessarily inherited, but it’s heritable. You can get the identical symptoms from really bad brain sagging. We had seen some patients over the years with that. But then we had one patient, and somehow he or his sister was related to this physician who writes articles for the New York Times. That was published, I think, five or six years ago, and then we started seeing quite a few patients with that.
These are people who not only have frontotemporal dementia signs but also a lot of other problems. Most of them sleep for many many hours a day, headaches, and earlier we talked about how 98% of headaches are orthostatic headache. But what I really should have said earlier is that’s a history of headache. So maybe not at the time that you see the patient, but when you ask their history, they’ll say, oh yeah, years ago I had a headache and it was orthostatic. But they also have lots of other problems. They have dysarthria, dysphasia. Some of them have feeding tubes in. They have tremors of their face or trunk or hands – sometimes their feet. They have trouble with hiccupping because of brainstem involvement. This is really an awful disease that sometimes we can help, but most of the time we’re not able to identify a CSF leak in those patients.
Interestingly, of all the ones where we do, 99% of them have a CSF-venous fistula. It’s almost unheard of to get this disorder from a ventral or lateral type of leak. Dr. Maya showed some of these pictures. These are the first three patients we saw with azygos vein stenosis. This is on the Feraheme MR venogram. These are the pre- and post-stenting venograms that Dr. Maya performed. The first two patients that we did this on did really, really well, within a few days of placing the stent. These numbers are from what I call the SIHDAS scale, the Spontaneous Intracranial Hypotension Disability Assessment Score. It’s just like the MIDAS scale, but instead of saying, how much are you bothered by your migraine headaches, I say, how much are you bothered by your SIH symptoms? I think this picture was shown as well.
What we think is that because of this high-grade stenosis of the azygos vein, the area of the azygos vein between the stenosis and the right atrium of the heart, the pressure is really, really low. It’s sort of like a sump effect, and throughout the day those patients, it’s like a giant vacuum cleaner that sucks in the CSF either through little fistulas or just through normal pathways. Because about 5% of your CSF is absorbed at the level of the spine. And we haven’t really seen any other patients with this since this was published. We’ve seen a few patients with orthostatic headaches. And there are a few we’re going to see in the next few weeks. But we haven’t really looked into this with patients who don’t have really bad brain sagging. But maybe that is another reason.
And then what I call skull defect, frontotemporal dementia, sagging brain syndrome. Over the years we’ve seen a number of patients who had the following clinical scenario. Usually these were young people who were in a really bad car accident, traumatic brain injury, sometimes some other type of brain injury, a lot of swelling, they had a craniectomy, where they remove a large part of the skull. They do pretty well. They get a cranioplasty, usually just the bone that they put in the belly is placed back. They make a great recovery, almost back to baseline neurologically, and then years, decades later, they develop this frontotemporal dementia symptom, brain sagging on MRI, and the first four patients we saw, that’s what you see here. On the left side of those four patients you see the cranioplasty, you see the brain sagging, and you see the underlying destruction, the encephalomalacia of the brain injury. None of those patients were treated.
But then about a year and a half ago, within a few months really, we saw four other patients. The first patient, his mom said, you know, is there anything you can do for my son because he does not have a wife, he had to go to a nursing home, he was only 27, and he had what looked like a pretty good cranioplasty. I said, well, I guess we could put in another cranioplasty, maybe he’ll get better, and he miraculously did get better within a few days of surgery. And then the subsequent three patients also did really well, except for one because he hadn’t had any other treatment for CSF LEAK. This is just a video during surgery and you see it looked like a pretty good cranioplasty.
And the other thing that they exhibited is that when you saw them either in the hospital—a lot of these have to be transferred from hospital to hospital because they can’t really go by their own accord—or in clinic, they all have this repetitive flexion at the waist, once a minute, sometimes 10 times a minute. They constantly do that. And I think I have a video of that. They do this like all the time. And that’s what we call compulsive repetitive flexion. That’s at the waist, and then they oftentimes have breath holding with it. And Dr. Schmahmann came up, who’s a neurologist at MGH, and we call that CoRFBiS. So that’s compulsive repetitive flexion with breath holding and sagging brain syndrome.
As a matter of fact, Dr. Kranz showed that to me earlier. There was an article that was just published in Neurology, which is a pretty good journal, and that shows this. It describes a patient just like this, and they say, oh, this patient had a midbrain malformation, a congenital malformation, but actually what the MRI showed was really bad brain sagging. That happens not infrequently.
And then actually one of these patients that I just showed you, because he underwent so many testing at the hospital, he wasn’t able to do this constant flexion, and then actually his cranioplasty depressed and it became what’s known as the sunken scalp syndrome.
And then this is what their cranioplasties look like at the time of surgery. Not a really good cranial, I mean a decent cranioplasty when you first look at it, but it’s a little wobbly. It’s not really secure to the surrounding skull. And then this is what it looks like before and after we do this implant, a PEEK implant, which is a custom-made plastic implant, and these patients have done really, really well with that. So that’s something that you also can consider.
Since we published that, we’ve done it a few other times. This is a young girl who had that and her brain sagging resolved. But this is actually the same girl where we also fixed her skull base CSF leak. I usually don’t like doing two surgeries at the same time, but because she was so young, we thought we would fix her skull base CSF leak and revise her cranioplasty.
This is a lady who had subdural hematoma evacuation. She had this fistula. We operated on it. She felt better, but not completely better. And that piece of bone that you can see there, right? There’s a little plate that’s sticking up in the air, and when you would compress it, it was also a little wobbly. She had a cranioplasty done near where she lives that you can see there on the right, and then her orthostatic headaches resolved.
This is a patient of Dr. Maya who had some congenital abnormalities, very positional headaches. Dr. Maya did a whole bunch of DSMs on him, didn’t find a leak. But he had no bone on the right side of his skull. So then he had a cranioplasty placed that you can see there, and his orthostatic headaches resolved.
And then I asked a few CSF leak centers if they had seen similar patients. This is a patient who was seen at Duke and the University of Toronto. This was a young man, same scenario, had really bad traumatic brain injury, did great after cranioplasty. Years later, he had all the symptoms of frontotemporal dementia, really bad brain sagging. It actually was so bad that he developed this cyst in the midbrain. And then here the cranioplasty still looks pretty decent, but now he actually fractured. He didn’t fall, but it just spontaneously fractured. But he lives in a different country, and a PEEK implant is pretty expensive. In the US they charge about $8,000 for it. So he’s waiting for that to be approved, the surgery for that.
That’s sort of the different type of other problems that you can look for. Maybe it’s not in the spine, but that’s really rare. That’s like less than one in a thousand pooling of CSF. It’s kind of difficult to diagnose, but it’s certainly possible. Sometimes I remove—if somebody has bad dural ectasia—remove some of the dura and then try to suture it back. But usually the dura is so fragile that it doesn’t really hold the sutures that well. And then you can look into these very innocuous-looking tiny little blebs on the lateral portion of the dural sac. And at least in our experience, all of those represent one of these two types of CSF leak.
You could look for azygos vein stenosis. We really only do it on a routine basis in patients with bad brain sagging. And I think if your patient has a history of a craniectomy, even if the cranioplasty looks like it’s very functional and well-placed, I would have a really low threshold in replacing that with a PEEK implant, just because there’s the potential for providing so much benefit to these patients. Thank you.