Dr. Wouter Schievink at the 2023 Cedars-Sinai Intracranial Hypotension Conference
Dr. Wouter Schievink, Professor of Neurosurgery at Cedars-Sinai in Los Angeles, CA, presented this talk on “Clinical mimics: Behavioral Variant Frontotemporal Dementia and Bibrachial Amytrophy” at the 2023 Cedars-Sinai Intracranial Hypotension Conference on July 8, 2023. The conference was hosted by Cedars-Sinai with generous support from the Spinal CSF Leak Foundation in Kohala Coast, Hawaii.
Slides from the talk
View a PDF of Dr. Schievink’s slides here.
Transcript
Dr. Wouter Schievink on Clinical mimics: Behavioral Variant Frontotemporal Dementia and Bibrachial Amytrophy:
[00:00:09] So good morning again, everyone. I’m going to talk about two very serious sort of sequela of chronic CSF leaks. That doesn’t have too much to do with headache. You know, in the title it says bvFTD, BBA, and it’s like as if everybody would know what that means. And that just shows you that I think particularly in our conferences, right, we’re all like super fascinated by CSF leaks.
[00:00:43] But that’s not shared by 99.99% of other physicians. So, as Dr. Wong and Dr. Friedman already alluded to, and we all know, headache is by far the most important and the most frequent symptom of SIH and when we tabulated that in about 200 patients who we saw in a certain year , it says 98.5% of people have headache, but that’s not necessarily acute headache, or even a present headache or an active headache. It could also just be an history of headache.
[00:01:20] And then as you know, I think Dr. Wang already showed this slide, there are quite a few other non-headache related symptoms that patients mentioned, and again, it doesn’t have to be an active symptom, it can also just be a history of a certain symptom.
[00:01:36] And I’ll just talk about these two, behavioral variant frontotemporal dementia, and then bibrachial amytrophy. So what is behavioral variant frontotemporal dementia? That’s really an idiopathic disease. It’s genetically based. It often runs in the family. It’s incurable. It’s manifested by progressive deterioration in personality, social comportment.
[00:02:00] I think comportment just means behavior and cognition, right? And when these people get an MRI scan, you see very severe atrophy of both frontal and temporal lobes. Like I said, it’s incurable. It’s a horrible disease and most people don’t live more than a few years after the diagnosis is made.
[00:02:20] Now, a couple of months ago, there was a famous actor in the news who has frontotemporal dementia, but he does not have a CSF leak. He actually does not have this behavioral variant. There also are other variants of frontotemporal dementia that we will not go into. So it was quite remarkable that now, and it’s already two decades ago, that Dr.
[00:02:41] Hong and his friends published a single case report of a patient with severe brain sagging who was found to have a CSF leak, who had symptoms totally indistinguishable of those symptoms of behavioral variant frontotemporal dementia. And since that was published, we’ve seen more and more of these patients.
[00:03:03] And in order to make the diagnosis, you can look up these different diagnostic criteria. The clinical diagnosis is just based on symptomatology, and it’s mainly behavioral disinhibition, it’s apathy or inertia, loss of empathy, preseverative behavior, hyperorality. And then when you do neuropsych testing, there’s usually loss in executive functioning.
[00:03:29] So it’s usually, as we all know, it is difficult to capture any type of behavioral disinhibition in your patient. You know, they might have been on the news or something like that, but it’s difficult to capture it during an exam. But that happened with this particular patient:
[A video plays, with an off-camera voice instructing the patient]
Off-camera voice: “Alright. Hold straight out.”
Patient: “Hey, douche, that’s what I’m trying to do.”
[00:03:59] So, you know, obviously he has more going on than just that. And for those not in America, that word that he used, that’s really not something you would ever say to anybody in polite company. By the way, this was not directed at me. This was directed at his father. So, another feature of this is apathy, right? Or inertia. So, this is an example here.
[A video plays, with an off-camera voice instructing the patient]
Off-camera voice: “What can you say?”
Patient: “I can’t say much.”
Off-camera voice: “How come?”
Patient: “I don’t know. [unintelligible]”
Off-camera voice: “You don’t know?”
Patient: [unintelligible] And he came down [unintelligible]. Yeah.
A second off-camera voice, commenting to the physician: “This what he does all day now.”
Physician: “Yeah.”
[00:04:59] So as you can imagine, we only see these people who are neurologically devastated if they have a super supportive family or friend system, right? Because otherwise they won’t show up in your office. You know, I think a lot of these patients are either in jail or they’re in nursing homes.
[00:05:17] And this is another example. So this gentleman would literally sit in a chair doing nothing for two or three hours. Another typical type of inertia is that they’ll like keep on brushing their teeth for 10, 20, 30, 40 minutes unless somebody tells them to stop doing that. So that’s the apathy and inertia.
[00:05:42] Another symptom is this perseverative behavior. And Dr. Shaman who’s a neurologist at MGH called that ROFBIS, which stands for repetitive obsessive flexion and breath-holding in sagging brain syndrome. And this is an example of this flexion that people do.
[00:06:02] It’s at the trunk. It’s at a very acute angle. And they just keep doing that. I don’t have a real good example of breath holding, but it’s something like that. But then usually it, it lasts a little bit longer.
[00:06:18] And then even though it looks like these people are devastated and at maybe even the end of their life, right? Like, like this gentleman. So if you’re lucky enough and you find a leak or you do some other procedure that’s indicated for a CSF leak, the patient actually can do really well.
[A video of a patient plays: “I felt better after my surgery and I’m doing really…”]
[00:06:39] So unfortunately we usually are not able to detect the leak in these patients. We’ve had the opportunity to see quite a few of those patients and I think part of it is just about publishing that in the literature.
[00:06:55] We saw a lot of patients after one of our patients was featured in the New York Times magazine, and we’ve seen about 51 patients with this. The mean age is, as you can see, it’s in the sixth decade of life, right? So that’s like the typical age for frontotemporal dementia.
[00:07:13] Only one of these patients had an obvious leak that you could see on a spine MRI or that you could have seen on a CT myelogram. Thirteen patients had this specific type of leak that’s called a CSF-venous fistula. But in most of these patients, we were not able to actually detect the spinal CSF leak.
[00:07:32] So that either means that our technology isn’t good enough yet or it means that maybe there’s some other way that there’s just not enough CSF within the spinal space. This is from our first, I think, 29 patients, and it’s a really busy graph, but what I want you to pay attention to is the dark blue.
[00:07:52] That’s the time period of typical SIH symptoms, right? So usually they present with a headache. And then later on after months, years, that headache kind of goes away. And then they start with their symptoms of behavioral variant and frontotemporal dementia. But you know, there also is an occasional patient who just has frontotemporal dementia symptoms and never really has a symptom related to SIH otherwise.
[00:08:20] What’s interesting is that, and it’s a small minority, but some of these patients are like the [patients in] the videos I showed you, but then within minutes or hours of lying down, they appear to be totally normal, and then within a few minutes to hours of getting up they revert to their state of frontotemporal dementia.
[00:08:39] Obviously, you don’t see that in the idiopathic form of frontotemporal dementia. Something that’s always present in these patients is this daytime hypersomnolence. We’ve seen that in everybody with brain sagging and frontotemporal dementia. But there also are a lot of other symptoms that you can see with sagging brain syndrome.
[00:08:59] This lady does not have frontotemporal dementia, but she does have severe brain sagging. And one of the things is that their speech is really slowed and it has an altered pitch. And this lady also has some tremors.
[A video plays of a woman speaking very slowly and with difficulty]
Patient: “Now you said it’s not [unintelligible] it’s not going to get better?”
[00:09:30] And then after surgery:
[A video plays of the same woman, alert and speaking normally]
Patient: “Okay. This journey has taken four years. Dr. Schievink has helped me…”
[00:09:38] And you can see that she still has this sort of hyperactivity in her hands, but no, certainly her speech is a lot better.
[00:09:53] And then that was that gentleman who was somewhat disinhibited and his dystonia resolved after surgery. Now there are some really common barriers to making this diagnosis, and I think the most common one is just misinterpreting the brain MRI. So invariably, these patients have really severe brain sagging and we think that at least partially that can explain their symptomatology in that the connecting pathways of the frontal and temporal lobe are disrupted. But maybe something else is going on, and I think Dr. Stoodley might be talking about that later today. But these are two patients with frontotemporal dementia, severe brain sagging. Both of them were diagnosed with a congenital mid-brain malformation.
[00:10:37] One of them was treated with a a VP shunt. I think that patient passed away shortly after that procedure. Then this patient was diagnosed actually with a mid-brain glioma. And they were going to do a biopsy. At first they thought, I will just radiate it. And then they happened to have a really good neuroradiologist at their brain tumor board and he said, “Oh, this is not a glioma.
[00:11:00] This is brain sagging.” Another barrier, and that’s really more on us, is that it’s really difficult to find the source of the of the spinal loss of CSF. And in our most recent study, we found that really only in about two out of five people are we able to detect the exact location and type of the spinal fluid leak.
[00:11:25] So now bibrachial amyotrophy, that’s a totally different disease. It’s a progressive, painless weakness and atrophy almost always affecting the musculature of the shoulders and the upper extremities. In the end it’s always bilateral. But in the beginning it may be just unilateral and certainly the muscular weakness and atrophy can be asymmetric.
[00:11:48] Oftentimes they have fasciculation. So it’s no surprise that oftentimes these patients are diagnosed with amyotrophic lateral sclerosis or Lou Gehrig’s disease or person-in-the-barrel syndrome. And it’s always associated with a very extensive extradural CSF collection. So unlike frontotemporal dementia, brain sagging, where we almost never see that, in bibrachial amyotrophy we always see that.
[00:12:16] These are just some examples of that. Here you can see that there’s tremendous loss of musculature in the shoulders and upper extremities. This lady has, there’s almost no muscle left in her upper extremities. This was a young gentleman who actually had his leak at age 19.
[00:12:33] Then he developed the bibrachial amyotrophy. You can see that although after surgery there was some improvement, there’s a lot of atrophy still in the hand musculature. But he was able to become a police officer. Sometimes it’s a bit easier to show on the video.
[00:12:52] That gentleman and then this lady—it’s almost like she has flippers because she really has no muscular strength in her arms at all.
[00:13:03] So we’ve seen 20 patients with this disorder. So it’s really rare. There’s like 20 out of more than 1800. Five patients really had no history of an orthostatic headache or other symptom of SIH. So we don’t really know the relationship between the onset of the leak and when this bibrachial amyotrophy starts.
[00:13:25] But for the other patients the mean age of onset of SIH symptoms was pretty young. There were only, the mean age was only 26. You know, there’s a pretty good range. But in five patients their CSF leak started in adolescence. And oftentimes there’s a more or less trivial type of traumatic event that precedes that.
[00:13:47] And the interval between when the CSF leak starts and when the symptoms and signs of bibrachial amyotrophy starts, it’s pretty wide. In our series it’s as early as one year and as late as 39 years later, but on average it’s about a decade. So on average, there’s about a decade between when the leak starts and when bibrachial amyotrophy starts, and we do think that the results of fixing the leak are much better. If you get to it the sooner the better. But the cutoff seems to be about 10 years.
[00:14:23] We know a little bit about what the actual risk is of a developing bibrachial amyotrophy. So we studied a group of patients with leaks in front of the spinal cord, ventral leaks. We’ll talk about that later. And then we found that about 20% of those patients after 15 years had developed bibrachial amyotrophy.
[00:14:44] But you know, to be honest with you, that’s really, that’s only two patients out of the 60, I think that we follow. So, you know, it’s not totally negligible but obviously it’s not that common either. You know, unlike superficial siderosis, so this is superficial siderosis on the left, and Dr.
[00:15:02] Harris will talk about that later. In superficial siderosis, right, there’s about a 50% chance of developing that after about 15 years. So, what are the common barriers for not making the diagnosis of bibrachial amyotrophy? I think really the most common one, and these are examples that are pretty recent, is that it’s just not recognized on the MRI scan.
[00:15:28] So, for example, on the left side and actually the neurologist wrote on the indication is there a CSF leak because he really suspected a CSF leak. And unfortunately this MRI, even though you can see the ventral collection— there’s a C1-2 retrospinal collection—it was read as a normal scan.
[00:15:47] This was that police officer that I showed you earlier. And then this one in the middle as you can see here, there’s a pretty large ventral collection that was read as degenerative disc disease. So that patient ended up with a cervical discectomy infusion. And then this MRI scan on the right side, you can see the extradural CSF, but this happened after a fall, so that was read as an epidural hematoma and that patient underwent pretty extensive spinal and cerebral angiography
[00:16:21] before the correct diagnosis was made. And the other kind of typical thing that we’ve seen is that people recognize that there’s a ventral collection, but it’s it’s interpreted as showing some type of congenital cysts, like you can see here, right? These are ventral leaks. Some of them are very large.
[00:16:40] And they say, yeah, that could not cause just bibrachial amyotrophy, right? Either it would be a myelopathy. But so the reason that people get this is that this collection in front of the spinal cord really stretches out the cervical and upper thoracic nerve roots. And actually not all of these patients have a leak in front of the spinal cord.
[00:17:02] It can also be on the side of the spinal cord. And then another common barrier, and that’s really more onto us, is that sometimes it’s difficult to localize the exact leak site, or sometimes people of course don’t even look at it. So this is somebody who had bibrachial amyotrophy. It was recognized,
[00:17:22] it was recognized that it was probably related to this extradural CSF collection. So the neurosurgeon just did a cervical laminectomy. There was a lot of leaking, but of course that kept going on. Then they did a cervical discectomy infusion. They saw a big extradural CSF collection. They squirted in some blood and glue; that didn’t fix it; and they did another surgery that required a fusion.
[00:17:49] They couldn’t find it. And as you can tell here on the CT scan, there’s a little dot of calcium, of bone, there. And that’s actually what had caused the leak. This is from surgery. And then pretty soon after surgery that extradural CSF collection resolves. So, they both have in common that there’s an insidious onset, right?
[00:18:12] It’s not an acute onset of symptoms. Headache: by the time that they get these complications, usually that’s not very prominent anymore. Oftentimes it’s misdiagnosed. But what’s very different is that with frontotemporal dementia, there’s almost never any extradural CSF. But with brachial atrophy, there’s always a lot of extradural CSF present.
[00:18:37] Alright, thank you.