Slides
Transcript
Thank you. Thank you very much. Let me start by thanking the organizing committee – Wouter, Peter, and Jürgen. Thank you very much for this very kind invitation, and it’s lovely to see so many of you here on this Saturday morning when there’s lovely weather out here. This is far more important than the lovely weather out there. It’s good to see you here.
So I was asked to talk about the impact of spontaneous intracranial hypotension. I changed the title a little bit. I made it multi-dimensional because that’s what I want to talk about – about how multi-dimensional this is.
This is my disclosure statement. I’ve been wined and dined a lot, but hopefully not corrupted. The only thing that I think is relevant on this is that I’m the president of the medical advisory board of the CSF Leak Association. Other than that, all of these are non-relevant.
So why even talk about spontaneous intracranial hypotension? What captures it for me is that when we were doing a survey, which was led by Sanjay Cheema, who is in the audience, and by the CSF Leak Association in the UK — we have the representatives over here, Claire Joy — one of the testimonies I got from the patients said the following:
“Being sent home by doctors to lie in a bed for months on end with no support, no job, no life, is soul-destroying.”
And I’m sure all of you relate to this, because I’m sure you are all aware we hear of this day in, day out. And that, for me, captures the essence of what the problem is over here. That it has an enormous personal toll for our patients, and it has a cost. And that cost is not just personal, but there’s a societal cost — whether it is to the healthcare system or whether it’s to society in general — and that impact is really significant.
And to me, it actually highlights that there are some care gaps – important care gaps – that really need addressing. And that is what I’m hoping to do. The roadmap I have for the rest of my lecture is going to be to talk about the burden and the impact that this condition has on our patients, the diagnostic journey that our patients have to go through, and what some of these management gaps may be, and also what are the results of the outcome and recovery that you can have from this. I’ll try and make it as evidence-based as possible as I can, albeit some of the evidence is often very sparse.
So what do we have in the way of available studies out there? So these are the seven studies that you can pick out from the literature. The first study was done by our group, as I was pointing out, by Sanjay Cheema, and then in the last three years we’ve had a plethora of studies come through. There are seven studies out there.
The vast majority of these, as you will see, are cross-sectional studies. But we have a very interesting study from Duke, by Tim Amrhein. And even though it was a small study, it’s a qualitative study where they’ve actually gone and asked patients what is important to them. So this is not about what’s important to us, which can be different from what’s important to the patients. And I’ll try and highlight some of those things that have been brought out – albeit it’s only in 15 patients, but that’s exactly the nature of qualitative studies.
And when you look at the rest of those studies, they are pretty cross-sectional surveys. So they’re going to have limitations. The limitations are going to be that it is dependent on patients volunteering. So there’s going to be a bias in terms of who volunteers. There’s going to be bias in terms of the patient recall in some of these studies, and there are going to be the usual kind of biases that are built into cross-sectional studies. But nonetheless, there are some important messages that come through. And also, I think very many of these studies do highlight what we do see, rather than actually picking up what is happening at every stage of the journey. It is really a cross-section of what is happening across the board in terms of what we see. But nonetheless, it’s a useful message that I think we’ll pick up from there.
So let’s just first ask the question: what is it that leads to disability? It was being pointed out to us a moment ago that the figures we have in terms of orthostatic headaches compared to what we see is a bit different. I think part of that bias is built into the fact that the International Classification of Headache Disorders have this criteria that you have to have a headache. So there’s a bias in the literature that very many of the cases that are actually described, or series that are described, had to have the criteria of a headache.
So we decided we want to really understand what the phenotype is of these patients. So we decided to look at 137 consecutive patients that we saw in other series. And this was a study that’s just been published by Dwij Mehta, who is another group. And this, I think, gives you a more accurate reflection of what very many of us see in secondary and tertiary referral centers. What we found was that orthostatic headache, in fact, occurs in about 75% of the patients — not the 92–93% that we see. And the vast majority of the others either have a non-orthostatic headache or simply do not have a headache at all.
So why is the orthostatic headache important? For the very simple reason that when patients say to you that they can’t either sit up — as we just said, a patient can’t even get the head off the bed — they want to be completely flat, don’t even want to have a pillow. And that extreme circumstance can also arise. And when these patients say they can’t be upright for prolonged periods of time, you can understand why they can’t be engaged in work or self-care.
And when we looked at our own data, what we found was that 59% of the patients — so 60% of the patients — the maximum period of time they could be upright was about four hours. And this is later on in the course of the journey for very many of them. At the early part of the journey, when the orthostatic headaches are even more severe, that figure is likely to be even higher.
And when we look at the impact of that on HIT-6, which is a standard headache impact test, then the average score was 68 out of 78, which is in the very severe disability. So on average, these patients have very severe disability due to the headaches.
What this study showed from the qualitative research they did is that the second group of symptoms that is really important is the audiovestibular symptoms. Patients have constant tinnitus. They get hearing loss. They get this fullness. And all of this disrupts your ability to concentrate, to communicate. It starts impacting your sleep as well, and increasingly socially isolates you.
I don’t know if any of you have ever had tinnitus. I have had tinnitus for a very short period of time. It was incredibly disruptive. I was sitting in clinic rooms and often could not hear my patients, and you then start realizing that we often dismiss tinnitus — so what’s the big deal? But it is really important when it’s particularly loud.
The third symptom that Tim’s group outlined in terms of what is important to patients was neck and interscapular pain. Even though the numbers we see are — and at least what’s reported in the literature — is low, I think that is simply because we do not ask about that question often enough. I think it’s far more important than we actually realize.
The other things that are important are nausea and vomiting. If you’re feeling nauseated most of the time, or you actually start vomiting, you simply do not feel like eating. And if you feel nauseated every time you’re upright, you try very hard to remain as flat as much as you can, which further compounds your ability to be upright.
And then the two things that I think are really underappreciated are cognitive fog and fatigue. We’ve heard about the extreme form of the dementias — the brain sagging pictures — those are relatively rare. What is very common is a huge number of patients come along and say that they simply can’t think straight. They have impaired concentration. They have a lack of mental clarity. Their memory is really poor. They become very forgetful. They simply cannot multitask.
So we specifically asked for those questions, and what we found in our series was 44% of the patients reported those symptoms. In fact, if you ask for any symptom, the number was much, much higher. When we asked for people who said that it was significant, it was 44%. And that just goes to show that I think we’ve underappreciated this symptom.
And the same, to a certain extent, applies to fatigue — that half the patients will report significant fatigue to the point that they don’t really want to get up and do a lot. And these again are high-value questions that are really worth asking patients.
And of course, over and above that, you have the visual disturbances. You can have double vision. You can have your blurred vision. And you can have all the sensory phobias. So it is not just about headache. It is a lot of other symptoms that start impacting a lot of patients and that drive the disability. And if you focus just on the headache, there’s a huge chance — there’s a huge risk — that we’re going to miss the wider picture, the wider spectrum of the things that drive the disability. So that’s where we are in terms of the clinical phenotype and how the clinical phenotype drives the disability.
But what do the quality-of-life studies actually point out? And what they show us is that there is a multidomain impact — that across the board, whether it’s physical, emotional, or social domains — all of them are affected. And it impacts not just on the headache, as I already pointed out, but mobility, self-care, the usual care that people can take of themselves, activities of daily living — but also starts impacting on other things such as their ability to interact with their families and their ability to work. And all of this often drives the disability from mental well-being.
There are multiple quality-of-life measures that have been looked at, but there are three I want to point out to you. There is the SF-36 scores, which came out of the US study. This was Deborah Friedman’s group that did the study. In fact, if you want to look for a quality-of-life study that is gold standard, Deborah Friedman’s group, I think, carried out the best study of all the various studies that are out there.
And the SF-36 scores, when they looked at both the physical component and the mental component, there were significant drops of 30 points in both of those measures. And these scores were significantly worse than multiple sclerosis and IIH. And also it’s been compared against advanced Parkinson’s disease, and the scores in fact are much worse than what we find in those conditions.
In our own study, when we looked at the EQ-5D survey, we found that 84% of the patients had major problems with usual activities. Pain drove the disability in 88% of the patients. Mobility impacted in 54%. For 39%, they were not able to self-care. And anxiety and depression was reported by 45% of the patients.
Another measure that has been looked at — and a very interesting measure — by Jürgen Beck’s group. They looked at the 15D. In fact, it was Jürgen Beck and the Swiss group. They looked at the 15D health-related quality of life in patients who are treated. So this is where you would expect some improvement after they’ve been treated. And yet even in that group — even in the treated group — we still have significant disability compared to the general population. And I’ll come back to that theme in terms of what outcomes are after patients have been treated.
What about the mental health impact? So I’ve looked at three studies over here. Again, starting with Deborah Friedman’s studies. They showed that 49% of the patients had significant depression, and 25% had anxiety. Our own study was actually very, very similar — 55% had depression and 38% had anxiety. This was significant depression and anxiety.
The outlier there is the Austrian study, where they said 78% of the patients had depression and 97% had anxiety. But when you read through that study, what you in fact find is, I think there’s a huge selection bias. It is, in fact, an international study where you had people from any country who could participate, and I think what happened is patients who were at the extreme end are the main people who participated. Hence, you get a bit of a skewed view over there.
Again, Deborah Friedman’s group showed that there’s a significant amount of hopelessness and suicidality in these groups. So 65% of the patients expressed a wish to be dead at some point, and 24% had actually engaged in some sort of a suicidal behavior. These are huge numbers.
I look after patients with cluster headaches. I’ve got a group of 1,200 — a cohort of 1,200 patients — which is considered, neurologists over here will appreciate, we call this suicide headache for a very good reason. These numbers are equivalent, if not worse, than what we see in cluster headaches. Which just drives home the message that this is really, really important in terms of the impact it’s having on our patients.
And then coming back to the cognitive fog — here again, I’ve already mentioned all of this, but again, a number of studies actually point out to it, though we don’t have the numbers from the other studies, but point out to the fact that memory lapses, difficulty concentrating, and health-related anxiety are really, really important in all of these patients.
And yet, despite having such a significant impact on their mental well-being, we found in our study in the UK that only 15% of the patients had actually had a formal referral to mental health services. So we are underappreciating what is going on with this patient group in terms of the mental health impact.
What is the occupational impact? Again, several studies. In the UK study, we found that 50% of the patients had to modify what they were doing to be able to continue working, and a quarter of the patients actually lost work.
In the Austrian survey—again, I think it’s a bit skewed because it’s more intractable than most patients—they said that only 15% of the patients were able to maintain full-time employment, and about half had to reduce to part-time roles. 32% percent were unable to work at all, and 6% took early retirement.
So the message over here is that here is something that is not only very impactful in terms of the disability it’s going to have while you’re having it, but even after treatment, there’s residual disability left that actually forces people to either take retirement or actually stop working for whatever reasons.
And the consequences, of course, from this are going to be economic, but there are also going to be consequences in terms of identity. Our identity is often tied into our occupation and what we do. And once you take that away from patients, unsurprisingly, a lot of patients talk about how it undermines their self-worth. And this is a message we hear all the time.
And it’s really important in this respect to start thinking of rehabilitation when we are trying to get these patients back into work—to actually speak to the employers and say to them what it is that is important to get them back into work. The graded return-to-work programs become really important.
And the social impact. A lot of this is what you can surmise really. Family and caregiver status changes. We see a shift. Partners suddenly become caregivers or the sole earners, and this often leads to emotional breakdowns. 32% of the patients report that it has a severe impact on their relationship, and the studies show that somewhere between 6 and 10% of the patients end up getting divorced as a direct consequence of having SIH.
42% of the patients say that it severely impacts their ability to engage in social activities – with friendships becoming more and more sparse, and they’re more or less isolated to their own environments. And understandably, it disrupts life in major ways.
So we hear things about people having to sell their homes and take career breaks, and all sorts of other impacts that illnesses can have. And what becomes really important is the support very many of these patients get from the patient support groups, which at least in our experience has been vital. You can feel very isolated, but having a group of people who actually understand you and being able to talk to them is a really, really important thing to do.
And what about the healthcare utilization diagnostic journey? There are a number of studies that have looked at this, and the message is very, very clear-cut. In the UK, you end up seeing three GPs before you even get referred to a specialist. You get referred to a specialist, and the first specialist who sees you — who is often a neurologist — misses it. Yeah, half the patients were misdiagnosed in the UK, very often having seen a neurologist and what is very often a stereotyped presentation.
Again, Tim’s study—just when speaking to those 15 patients—a common experience that was related was that there was a delay of months or years before SIH was recognized. So there’s a problem in terms of recognition. Then when patients do, they often end up getting a misdiagnosis and being treated for the wrong condition. But when it is actually thought about, then there are long delays to getting investigations done.
We found that from the time they request an MRI scan to it actually happening was an average of four weeks, which I thought by UK standards is amazing. I must confess, I thought it would be longer than that. But again, when I speak to colleagues, they say, “Oh, that’s appalling—four weeks for what is really an urgent condition.” And then look at the range over there. Some people – it took a year to get a scan. And again, for the blood patches, it can take four months to get a blood patch done, though on average it was about two weeks. And this is replicated across the board. You look at the Canadian study—it’s a very, very similar message that comes through, that there are long delays to getting anything.
And then having access to invasive imaging. You get your initial scan done. You may get the blood patch done. But after that, very many patients simply do not get referred on, despite the fact they haven’t improved. There are cases described of people getting seven or eight blood patches, but no referral for myelography or further investigations. And that’s across the board. It’s not just a Canadian experience. It’s an experience that we see across the board that we hear about all the time.
The Canadian series actually looked at how almost half the patients had no access to specialist services. But that is again true across the board in the various geographies that you look at.
And of course, the economic burden from this is going to be huge. 67% of the patients in the UK, and 81% in the Canadian report, said that they had major personal financial strain. 5% of the patients in the UK had to go about self-funding themselves because they could not, within the NHS service, actually get the resources for the pathway they needed to be on. And that figure was much higher, but we don’t have an accurate figure in the Canadian series, where very often people are getting money together out of pocket to go and get imaging and surgery from abroad.
And that is the personal cost. But when you start looking at the healthcare cost here—that we have to have multiple scans, multiple myelograms, we have got blood patches that need to be done, whether they’re targeted or non-targeted. Now we have venous embolizations coming through, and the surgery—and especially if people are on inappropriate pathways—you can imagine how those costs are going to multiply, and multiply very quickly. Somebody looking for a research project, this is something that is waiting to be looked at. Because I think what we’ll show is it’s very, very impactful in terms of healthcare costs. And the misdiagnosis also drives that cost.
So this has an impact—economically, personally, to the healthcare system, but to society in general—because of our pathways not being worked out very well.
And this is where I just want to put some perspective on the patient voice to this. I want to just outline three quotes that we have from our own study, which just outlines the importance of the work we do over here:
“Life completely altered for me and my partner. Had to sell a business, move to a smaller house. Partner currently on career break to look after me. We are severely restricted in finances and ability to live life. Don’t see friends or family much.”
Pretty much the messages I’ve put out already.
“I’ve lost my career… I’m mostly bed bound… I just want to be able to work.”
“Doctors only see the tip. The wider impact of a leak are numerous and severe, and support is all but non-existent.”
And the take-home message for me is this: that very many of these patients have a lived experience that we don’t appreciate, but I think the patient support groups do an excellent job in this respect. I think engaging and getting patients to engage with the support groups is a really critical part of what we do, because very often that kind of support can be provided by the patient support groups.
Just a quick comparative analysis here. When I looked at what the UK picture is, what the Canadian picture is, what the US picture is—slightly different healthcare systems. The UK is a single-payer thing. Very small parts of it are private. The vast majority is with the National Health Service. A very similar system in Canada, but a very, very wide geography. And the US—very wide geography, but very, very different. We have some excellent specialist CSF leak services that have actually given us a model about how we should structure a service, but yet we have big black holes where there is no cover at all.
And I think the messages that come through for me when I look at all of these various studies is that our barriers are exactly the same. It’s pretty much what I’ve pointed out—that there may be some differences in terms of our healthcare trade-offs. That with a single-payer, there’s less cost, but there are long delays. That when you have private healthcare, or when you have insurance-net, you get quicker access, but often the trade-off is that you don’t always get the access because there are barriers to that as well. So there are, I think, mainly barriers of the healthcare system structure rather than any overriding thing that actually tells us that there are significant differences between these systems.
I want to, in my final few minutes, just touch upon quality of life after treatment. Because it’s all very fine talking about how impactful this is, but can we improve quality of life of patients?
So again, coming back to Deborah Friedman’s study—they had in their cohort of 95 patients, 22 who were symptom-free, who had been through the journey where they had the treatments and were doing quite well. And for that reason, they were able to compare those patients with those who were still symptomatic. And what they showed was that those patients who were symptom-free had largely normalized when you looked across the board at the SF-36—that is, the physical component or the mental health component. When you look at the HIT-6, and when you look at your depression scores, they were close to being normal, although not necessarily completely normal. So there was a good impact with getting the treatments on board.
Then again, the German study looked at 80 patients here with spinal CSF leaks. And this is a study in which they showed what happens over time. That a significant portion of these patients started with a very high HIT-6, and when you look at them at 3 months, they’ve improved already quite significantly after surgery. And that improvement is sustained, if not even better, by the time you get to your 12 months.
So the messaging over here is: actually, yes, this may be very impactful when patients are disabled. But if we get it right and we treat them, our outcomes are likely to be very good in a significant portion of people. And that’s the positive message also that we must put out—that there is light at the end of the tunnel. If we get it right, we will improve quality of life for very many of these patients.
However, we also need to be careful that there are some residual symptoms that are left over. So from this same study from Jürgen Beck’s group—80 patients treated. The bit to look at is that red bit. We start off with a high proportion of patients here—in excess of 80% of the patients—who are highly disabled and aren’t able to be upright. But when you look at one year down the line, a quarter of the patients are still highly disabled, despite having had surgery, despite—at least from their perspective—these patients having had treatment.
And this is an area that we must still look at and think about, because these patients have got ongoing problems. And if we just focus on the headaches, we will miss the picture—that there are other things that often do not improve. And we need to look at this very, very carefully.
The Swiss and German study also did something very similar. They were really a survey after patients had been treated a couple of years down the line. And what they showed is that 52% of the patients still had residual symptoms. Half the patients, despite treatment, have residual symptoms.
See, part of this is historical, and things have got better over time. And I think that’s part of it. But I think part of it is what was being measured. If you look at the German study—if you look at HIT-6, HIT-6 is a headache measure. You look at what was measured in the Swiss and German study, and they used a score—which is in fact a global score—it’s a DF-15 score, and that looks at 15 different components. And I think part of the reason that that comes up with half the patients, or close to half the patients, have still got some sort of disability is that they were measuring what is relevant to the patients—not just the headache but other things as well. And I think this is where having an appropriate patient-reported outcome measure is going to be really critical for us in the long term.
So what are my take-home messages? SIH’s true impact is multi-dimensional. I’ve put some of the domains and some of the key impairments that go with that and that I’ve touched upon, but we must think of this as a multi-dimensional problem and not just a headache problem.
That timely standard of care is critical. You’re going to hear today about how, if you get in quickly—within 3 months—often outcomes are much, much better. And that is something that is really critical. That treatment restores lives, but often not completely. But nonetheless, very, very important we get it right as quickly as we can for them.
And to a certain extent, I think the call I would make over here is that we need a multi-disciplinary, patient-centered model, which includes the various disciplines: neurology, neurosurgery, neuroradiology, pain, anesthesia, psychiatry—very often missed out. And also we need to embed not only the psychological support, but the patient advocacy groups within our systems, because they’re a really critical part of what we do.
And for me, the next steps to really think about are: how do we disseminate pathways and guidelines that can be applied equitably across the UK, across the nations? And what are evidence-based guidelines? We need to build registries. Doing clinical trials, you know, is going to be very, very difficult in these patient groups. But registries do offer the hope of actually answering some of the really important questions. And if you can build national or international registries, that will be very, very helpful. And also we need to develop better treatments and better investigative modalities.
And I will finish off with what Wouter said to me when I visited him. Wouter, you may not remember this, but he said, “When we listen to patients and act swiftly, we don’t just patch leaks, but we help people reclaim their lives.”
And I want to finish off by thanking Wouter, who has been a source of inspiration for me over the years and was very helpful in helping me set up my service. A big hand to you, and thank you very much for having me here.