Transcript
Good afternoon everybody. Thank you. I haven’t even said anything yet. First I’d like to thank Dr. Schievink and the organizers for inviting me. It is wonderful to be here in Amsterdam and with all of you, especially to come here and talk about what I do every single day. My only disclosure is that I’m on the board of the Spinal CSF Leak Foundation.
As a neurologist and a headache specialist, I often see people, as do my colleagues out there who are in the same boat, who we really think in our heart of hearts have SIH. They come in with a very typical history. They get better in Trendelenburg. Everything sounds great except their imaging is normal and what do we do? It’s really, I think, quite a difficult situation to be in.
So how often is imaging normal in SIH? We actually have a meta-analysis poster that is outside that I invite you to come see. A group of us, 15 in all, did a systematic review and meta-analysis of papers that were published looking at imaging up through March 2023. And the reason we stopped at March 2023 was even though 15 people were working on this, we couldn’t even bear the thought of doing the literature search again. So we stopped.
What we found was that normal brain MRI was found in about 17%, which kind of goes along with what’s in the literature, roughly 20%-ish. Non-contrast spine MRI was normal in about a third. Radionuclide study was normal in about a quarter, and we didn’t really have enough studies on CT myelogram and digital subtraction to really get a good estimate. Importantly, we found that almost 70% of people who had a negative brain MRI actually had positive spine imaging. And conversely, about three-quarters of people who had a positive MRI of the brain had positive spine imaging, which was not quite statistically significant and, like most of the things in our study, had a high heterogeneity level.
So why would somebody who you really think has SIH clinically have normal imaging? Well, maybe—and the patients always wonder—maybe it’s just because I wasn’t leaking at the time. I think that’s possible. I think that there are some people that leak intermittently. Maybe they had a slow flow leak that wasn’t detected. Maybe they had a CSF-venous fistula that wasn’t detected. Maybe, as we heard this morning, there’s some problem with their dural compliance in the upright posture and they’re not leaking. I really envy y’all that get to see patients within three months of their onset of symptoms because that’s not who we see. We see people that are years out from their presentation, and even sometimes once they call the clinic, it takes months and months to get in. So maybe they just have long disease duration and the imaging findings tend to revert back to normal.
Our current imaging techniques are certainly getting better almost every day, but they still have limitations. They’re not perfect. There are people out there—not nobody in this room of course—who might not have the same experience interpreting the imaging or positioning the patient to do the correct imaging. Or maybe the patient has another cause of orthostatic headache, and that’s really what I’m going to focus on the most.
We know what we think of when orthostatic headache is mentioned, but this is the official diagnosis: occurs when the patient is upright, markedly relieved or improved in recumbent, often starts within 15 minutes of being upright but it can take hours to manifest, so-called end of the day headache, and the same thing with relief—it may occur immediately, but may take a while.
So there’s a pretty long differential diagnosis of orthostatic headache, but SIH is by far and away the most common cause. We’ll talk a little bit about POTS. If you think I’m going to give you a magic answer about how to distinguish these, I’m sorry to tell you that I probably will not. Other autonomic failure—I usually don’t see that. They end up in the movement disorder clinic. Upper cervical instability, third ventricular cyst, air embolus, cervical spine disease, and maybe even sphenoid sinus disease. There are a lot of case reports out there about unusual things.
A lot of the people that I see that I end up suspecting an SIH presentation, they get referred in because they supposedly have chronic migraine. So what do we mean by that? Chronic migraine: headaches more days than not, at least 15 days of the month for at least three months. The patient has a headache. At least half of those days it’s migraine. Come back here. The headache—no other cause identified when you look at the infamous ICHD criteria. All of the primary headache disorders have this little get-out clause at the end saying no other cause identified, with or without excessive use of acute medications. And I find that SIH patients are often misdiagnosed with migraine. And we found that in the study that we did on quality of life. And most of the time if you spend the time to take a detailed history of the patient, you’ll realize that they don’t have chronic migraine, but the symptoms are very similar.
So these are the SIH criteria for chronic migraine. It was mentioned before, but I just want to highlight it again. The ICHD was not meant to diagnose a secondary headache disorder. It’s not meant to give diagnostic criteria. When you look at the secondary headache disorders in the ICHD, which means it’s not migraine, it’s not tension headache, it’s not cluster, it’s something causing the headache, right? They all have a similar format. Patient develops a headache. Let’s say we’re talking about subdural hematoma. Patient develops a subdural hematoma. A subdural hematoma is diagnosed. It occurs in temporal relationship to the headache. The subdural hematoma gets treated, the headache goes away. Now, for almost everything in the ICHD, that’s how it’s structured. Headache, secondary diagnosis. Secondary diagnosis is treated, headache goes away.
There are only really two very important things in the classification system where they went so far as to try to put in criteria for the diagnosis of the secondary cause. Unfortunately, one of them is IIH and one of them is SIH. But that’s not the intention. The intention is to classify the headache. And so the discussion this morning was like, well, we see patients all the time that don’t have headache that have SIH and they say, well, it doesn’t meet the ICHD criteria. Of course not, because the ICHD criteria was meant to classify headache.
Okay, so back to the chronic migraine. You need at least two of the following: one-sided (we see this in SIH too), throbbing or pounding, moderate to severe intensity, worse with routine physical activity, and then at least one sensitivity to light, noise, or nausea and vomiting.
So how do you distinguish them? Well, chronic migraine usually evolves from not chronic migraine, less frequent migraine. Spinal fluid leaks generally come on at full force when they come on. Spinal fluid leaks may have a thunderclap presentation. Migraine does not. And importantly, SIH is orthostatic, right? It doesn’t, in my experience, get better with migraine medication, and it improves in recumbence.
Now migraine people will say—or, and I think this is a problem with asking the question the right way—the right question is not does your headache get better when you lie down. The headache in migraine or the headache in SIH is, yes, does your headache get better when you lie down, but you also have to ask the patient: when you lie down, do you go to sleep? People with migraine, when they lie down and they go to sleep, yeah, their headache gets better when they go to sleep. Okay, that’s different.
Okay, on to concussion. Again, a lot of overlapping symptoms. A lot of these patients, like SIH patients, are female. They may have a history of migraine, history of prior concussion. And most of the time they get headaches that are kind of migraine-like. That’s more common than tension-type-like, that’s more common than cluster-like. They’re usually bilateral. They’re usually moderate to severe in intensity, and they’re treated with medicines, as was mentioned from the first talk, like the phenotype describes.
But a lot of people with chronic concussion or post-traumatic headache have other symptoms that we see in SIH, like cognitive problems, sleep problems, vestibular problems, psychological problems.
There is some overlap in the symptoms, but there are things that distinguish them. Again, CSF leak orthostatic, post-concussion not orthostatic. The eighth nerve symptoms in TBIs are vestibular. We heard this morning about a lot of patients who have eighth nerve symptoms that are primarily cochlear hearing loss, and the symptoms that we see that are vestibular are usually imbalance. No cochlear symptoms in the TBI, but yes, you can see them with a CSF leak. Sleep difficulties: in TBI it’s usually insomnia. People with CSF leak may wake up because they have a headache sometimes, but they don’t really get that much insomnia.
Lastly, of the primary headache disorders, new daily persistent headache. This is the headache where the neurologists — we run to the door and try to leave the building when we find out we’re going to have to see these patients, because they are really tough to treat. Now, SIH is a secondary cause of new daily persistent headache. Patient never had a headache, they develop a headache one day, and it never goes away. Has to be present for at least three months. Usually sounds like migraine or tension-type and it is super, super refractory to treatment.
So what distinguishes them? Again, orthostatic. And then NDPH, it’s headache. There’s all the other things that we see with SIH, the vestibular problems. They don’t go along with having NDPH.
All right. Well, let’s go to the bane of our existence, which is POTS. It’s only the bane of our existence because it’s really hard to distinguish this from SIH. So, POTS is pretty common. In the US it affects about 1 to 2% of people. Typically, young white women. Usually they have kind of the package deal. They have mast cell activation syndrome. They have joint hypermobility syndrome. Often they have EDS. They often have gastrointestinal problems, particularly irritable bowel, and they often have migraine. The picture shows basically acrocyanosis, which they can get as well.
In order to make the diagnosis of POTS, the patient has to have at least a 30 beat per minute increase in heart rate for adults or a 40 beats per minute heart rate increase in children when they stand up, or an absolute heart rate of at least 120 beats per minute within 10 minutes of standing up. And they basically have—it’s an autonomic disorder. They have an abnormal adrenergic response when they stand up.
There are a lot of secondary causes of POTS. Medication is a big secondary cause of POTS and deconditioning is also a secondary cause of POTS. A lot of our patients with SIH, if they didn’t have POTS to begin with, if they’re having to spend prolonged times in bed, then they could have secondary POTS.
There are a lot of articles out there about the headache in POTS, and I really tried to find out what exactly is the orthostatic headache. And if some of you are POTS experts and want to chime in in the Q&A, I hope you do. But I looked hard and far to try to find a good article about what their headache sounds like because, as a headache specialist, that’s what we do.
The overall prevalence of headache in POTS is pretty high. It’s about almost 40%. And if you look in the literature, the orthostatic headache—this narrows it down, right?—anywhere from 2 to 60% is orthostatic. Well, what does that mean? Most patients have non-orthostatic headaches that have POTS. And most patients have headaches that are migraine.
A case-control study that looked at unfortunately only 9 patients with SIH and then 48 patients who had POTS identified that things that were more common in SIH included being diagnosed earlier, having an orthostatic headache, and neck stiffness. Things that were more common in POTS were syncope. Most patients with SIH, at least in my experience, they’re not fainting. They may have problems with their balance, but they’re usually not passing out. Worsening with menses, which is a migraine thing, and then myofascial pain. And neck stiffness in that study was only present in the patients who had SIH, so that was helpful.
There was a meeting last weekend actually in Minneapolis of the American Headache Society, and one of the sessions they had was on autonomic dysfunction. I submitted a question, which was done through a system. We couldn’t actually ask the question, so they couldn’t tell it was me, about what exactly does this orthostatic headache—how do people describe it? What’s the phenotype? And for people who get this orthostatic headache with POTS, how long does it take to go away? And the panel kind of looked at each other. One person said, “Well, my patients, it’s a coat hanger headache.” I almost fell out of my chair. It’s shoulders and neck and head. And I’m thinking, “How do you know your patient’s not leaking?” And nobody else really had an answer to that question. So I tried.
And this is super complicated. It’s hard to distinguish them clinically, and it’s hard to distinguish them even when you do testing. And we’re talking about people who have normal workup. So orthostatic vital signs and tilt table testing might be warranted. There are a lot of people who say you can just do orthostatic vital signs. They don’t need any fancy testing.
But unfortunately, they’re not conclusive because not all patients who have orthostatic headache will develop a headache when they’re on the tilt table test. And developing a headache when they’re on the tilt table test when they’re upright doesn’t necessarily correlate with having a headache at other times. SIH patients can also have increased heart rate with a head-up tilt table test and heart rate variability because SIH patients can also have autonomic dysfunction. So it looks just like POTS. And then as mentioned, POTS can also develop as a result of SIH. So which came first, the chicken or the egg? Is it the SIH, or the physical deconditioning could cause the POTS, or is it the POTS and they happen to have joint hypermobility which caused the SIH, and it’s just this whole big quagmire.
So what helps us? Not a heck of a lot. Eighth nerve involvement: again, POTS usually it’s lightheadedness, presyncope, sometimes syncope. SIH it’s usually true vestibular, like spinning dizziness or imbalance, and then cochlear dysfunction. So if you can get that history, that helps you, and after that it’s like I don’t really know, just kind of pray that the imaging really is normal.
What about hypermobility syndrome? Hypermobile Ehlers-Danlos, which you heard a little bit about previously, is the most common form of Ehlers-Danlos. There’s no genetic test for it, and it can be generalized, peripheral, localized, or just I was really hypermobile as a child, which I always ask people. And it requires at least one of the following: there’s a history of joint subluxations or dislocations, impaired proprioception, persistent or chronic pain, early joint degeneration, and soft tissue injury. But these patients with EDS and joint hypermobility, they also have headache a lot. They also have POTS. They also get anxious and depressed with all of those symptoms that go along with POTS, MCAS, fatigue, you know, this whole kind of package deal that we see. It’s pretty common, and about a third of patients with EDS or hypermobility will have headache as their primary complaint. Migraine is the most common cause of that headache. And there is a study that was recently published that looked at POTS, hypermobility disorders, and MCAS and headache, and the link for it is on there.
So what about those headache features? SIH usually comes on suddenly, right? People will often say it’s not necessarily throbbing and pounding and unilateral. They often, at least to me, say it feels like my head is being pulled down in my skull. They have this definite orthostatic or end-of-the-day, worse-as-the-day-goes-on kind of headache, usually with neck pain, often with interscapular pain, and worsening with Valsalva. And then there are some other features like eighth nerve that can help us out as well.
Patients with POTS, it’s usually throbbing. It’s migraine-like, frontal or global, and they have orthostatic intolerance. So everything feels worse when they stand up. They stand up, they get dizzy. They stand up, everything just feels terrible. So it’s not just the headache that feels terrible.
This is kind of—somebody mentioned it earlier—cranio-cervical instability. This is still kind of a gray area and a little bit controversial. There are no clear headache features described with CCI. The really bona fide cases tend to have brainstem symptoms or a cervicomedullary syndrome.
Next is cervicogenic headache. A lot of people talk about this. I’ve seen patients who I think have it. When you go to the literature, there’s just not much to find. Duke University, I know you’re out there. Please report your cases. I talked to Linda about this a long time ago. Hasn’t happened yet. Typical cervicogenic headache usually comes from the upper cervical roots and it’s unilateral. Sometimes it switches sides. It can sound like tension type. It can sound like migraine. It’s kind of all over the board. It sometimes radiates through the arm or the shoulder. It can be triggered by neck movement or certain head postures, particularly extension of the neck, and associated with limited range of motion. Peak incidence is in the seventh decade, usually arising again from the upper cervical cord, but there are some cases out there that it starts from C4 or below. The ICHD criteria say it should get better with anesthetic blockade. Well, a lot of people don’t get better with anesthetic blockade. Orthostatic headache has been attributed to axial loading in the upright posture with cervical spine disease, but again there’s not much in the literature.
So conclusion, of course I have to put my opinion in too: if the history sounds like SIH, I think it’s probably really SIH.
And the closest mimic I have seen is cervicogenic. There was one patient that actually went to Duke who had a missing part of his vertebral body at C4-5, and once he had surgery that fixed the problem, but I have a very small N.
The associated symptoms besides the orthostatic headache I think are the things that really help us to distinguish them. In my experience, SIH headaches really do not respond to migraine drugs, except maybe caffeine-containing drugs. And I know you heard about caffeine earlier, that it doesn’t make sense because caffeine really, at least in animal models, lowers CSF pressure. But some of my patients do get better with caffeine.
I would just say for those of you who are not neurologists out there, collaborate with a neurologist or a headache specialist and don’t give up. I think what the patients are most afraid of is that my imaging was negative and now what am I going to do, and everybody’s just saying, “I don’t know. Go see somebody else.” So don’t give up. Stick with your patient. Reimage them from time to time. You probably might really find something.
I just opened an office about a year ago, a solo office, and it’s got kind of a Texas theme to it. And I have the cowboy creed and the cowgirl creed signs up in my office. And this is the cowgirl creed: be strong when you’re weak, be brave when you’re scared, be humble when you’re victorious, and be a badass every day. So, I try to be a badass every day. And I know that y’all are badasses every day because you’re here at this meeting to try to help these people get better. So, thank you for your attention.