Extreme headache pain that comes on abruptly (the “thunderclap”) can signal a number of serious conditions – such as subarachnoid hemorrhage – or have a simple cause such as sexual activity or a change in medication. Neurologist Morris Levin, MD, director of the UCSF Headache Center, sorts out the diagnostics, offering the workup steps that he uses in practice and a display of what you may – or may not – see on imaging exams.
I am mo 11. I'm, uh, the, uh, director of the headache center at UCSF. So these are the topics I wanted to get through. I'm going to share a case with you. That's clearly a sex related headache. Then I'll define what thunderclap headache means. And then we'll get into the bulk of, um, the topic, which is all the different kinds of headaches that can present suddenly, which is what thunderclap headache is. We'll revisit sex related headaches and then I'll share with you kind of a simple approach to making the diagnosis in these headaches. And as we go along, we'll actually be talking about management. These are my disclosures. Um, I do consulting for different companies. I'm not on any company's payroll. I'm not a I don't do speakers boards. Um, I do get some royalties for things I'm written, and I've gotten some grants. So here's our kind of, uh um, quintessential case. This isn't really a picture of this patient, although this is a real patient in description. Um, he's a 28 year old guy who experienced a sudden headache at the time of orgasm that quickly became very severe, and it was so bad and so persistent that he was brought to the ER by his partner. He has no history of headaches. Mother has migraine cat scan of the head was done pretty quickly. It was negative. LP was then done. That was negative. C t angiogram was done. That was negative. And an m R venogram was done. And that was negative. So this is a case that you made this the kind of case you may encounter, And, uh, hopefully by the end of the our, you'll feel much more comfortable in handling this kind of thing. So what does the word thunderclap mean? It means a clap of thunder, of course, but it can also mean something sharp, loud or sudden. That's where the word thunderclap headache comes from. And here are several definitions of that. Here's the one from, uh, probably the best headache Textbook. Wolf's headache. Severe and explosive headache Maximum within 60 seconds. I wrote my own textbook in emergency neurology. Um, and I called a sudden severe headache and, um, principles of neurology, one of the best neurology textbooks. The headache of subarachnoid hemorrhage more specific. So the key feature that differentiates thunderclap headache from other headaches is its rapidity of onset. And it's not that rare 43 per 100,000 adults every year. So there are a lot of different headaches that you might think of when you start thinking thunderclap headache. What about worst headache of my life? Knife through my head? Horrible headache during sex, I think Horrible headache during sex qualifies, but not the worst headache of a person's life that may not have been sudden, um, a sudden, instantaneous headache. We don't refer to that as a thunderclap headache. That's just like a stab. How about how about I sensed an explosion in my head that's non painful? No, that's not a thunderclap headache, but a sudden neck pain, which is persistent, can sometimes be a thunderclap headache. And I'll hope to convince you of that horrible headache which woke me up. Sure, a really bad headache after I hit my head. No, that's not a thunderclap headache. The quintessential thunderclap headache is, in fact, subarachnoid hemorrhage. We're going to see a lot of other causes of thunderclap headache, but this is a quintessential thunderclap headache. What are the clues? Neck stiffness, nausea, vomiting, elevated BP and a CT scan showing blood, and I hope you can see my pointer. I'm pointing to blood and what are called the subdirectories cisterns looks like a star with these spokes. And there's another thing you see in this picture these two dark areas. Those two dark areas are the temporal horns of the ventricles of the lateral ventricles, and they shouldn't be seen that shouldn't be seen unless someone has hydrocephalus. And they're seen in subarachnoid hemorrhages because the blood blocks the flow of spinal fluid and causes a little bit of hydrocephalus and a lot of cases. So there are a lot of signs here that this person had a subarachnoid hemorrhage. The pitfalls in diagnosing these things are that CT scans can sometimes not show the blood they can be falsely negative. In other words, in 5% of cases in the 1st 24 hours, Um, then another thing that can happen, as you well know, is a lumbar puncture, the which should show blood. And if it does, that's supposed to be a sign that there was a subreddit hemorrhage. Well, what if you accidentally hit a vein as you're going in to do the lumbar puncture. And that's supposed to cause blood in the first tube, less so in the second, to less so in the third gym and so on because the bleeding stops after you've nicked that little vein. But that's not always true. All right, Sandra Chromium. Here's another interesting, um, piece of information. San through Crimea is a yellow tinge ng of of the CSF due to bleeding due to breakdown of blood cells. And it's a it's a Xanthia, chronic meaning yellow color. However, that doesn't happen until about six hours after the subarachnoid hemorrhage occurred. Takes some time. In other words, for those red blood cells to break down and liberate heem which is, you know, going to color the CSF yellow even when you diagnose sub record hemorrhage. Like in this case, this picture here, the aneurysm that was remark was responsible for it is not has never found what does that mean? Did it obliterate itself when it bled? That's a possibility. You know, these little aneurysms can suddenly just go when they when they blow, and, uh, they are not seen on angiography. Um, so do we have to keep looking because, of course, what we want to do is keep that aneurysm from bleeding again or and look for other aneurysms. Well, when do you do spinal angiography to look for an aneurysm that's not actually even in the brain but in the spine? This can cause some record hemorrhage, but we only do it. It turns out, if there's focal sub record hemorrhage, because just empirically, we only see these aneurysm bleeds from the spine when the blood in the head is focal, not all over the place. Like this picture. Here's a concept that we talk about a lot. The Sentinel Headache. People who have had some record hemorrhages often have a headache at some point before that subarachnoid hemorrhage we have to take seriously, because if you have a patient with a sudden headache that then maybe goes away, don't take it seriously. That could have been the time. That could have been the very nice early warning sign that led to the discovery of an aneurysm and surgical repair of it, preventing maybe even a fatal subarachnoid hemorrhage. Something like up to 40% of patients recall a headache or a series of headaches before their subarachnoid hemorrhage, probably due to these little hemorrhages, so called sentinel bleeds or sentinel headaches. They're not big. They don't show up on cat scan a lot of times. And in fact, an MRI study of 127 patients with subarachnoid hemorrhage found evidence of previous little bleeds Focal E, and about 11% were recalled by the person. Then there's another complicating factor. There are people who have sudden thunderclap headache who have an aneurysm. But it didn't it didn't rupture. It didn't bleed. So what's going on there? Well, Neil Raskin, at UCSF many years ago in 1986 described a series of patients. And this is one. This was a 1st, 1st case who had terrible headache, thunderclap headache and no aneurysm was ever found. No subarachnoid hemorrhage was ever found, but later the aneurysm was seen, and it was postulated that these aneurysms can enlarge and they can cause a sudden headache. Thunderclap headache without ever hemorrhaging. I'm sure you're thinking what I've been thinking for years. Which is that Okay, if these aneurysms can can cause a bad headache, a thunderclap headache without bleeding, shouldn't we do an angiogram and everybody and we're still not sure whether that's a smart idea or not. All right, let me share another case with this is a real patient again. Not the real picture. 38 year old woman with no headache history who had several severe, rapid onset so thunderclap type headaches over the last two weeks. She's now the ER, complaining of her latest one of these, which occurred while riding her bike. Stress has been high, and she just changed her oral contraceptive pill neck is supple, so not consistent with typical subarachnoid hemorrhage. Supple neck general examined labs are 100% normal. Neurological exam is normal, including endoscopic exam. CT scan was normal. Lumbar puncture was negative until the CSF comes back after spectrum. To Tom, a tree showed a yellow tinge. It wasn't apparent to the naked eye, but the specter of Fatima Tree machine showed a little bit of yellowing. So breakdown of blood cells in the CSF, which is abnormal. What happened? So looking back at that C t there actually was an abnormality, and I don't know if you can see it. I'm going to circle it with my pointer. This area here shows what we call a focal subarachnoid hemorrhage. It's not anywhere else. And if I were to show you other levels of that CAT scan, you wouldn't see that star shaped subarachnoid cisterns filled with blood image. You've seen just this little area of focal hemorrhages, right in a right in a sulk us on the surface of the brain and the Left Hemisphere. What is it? Well, it turns out that this is a cardinal manifestation of something called reversible cerebral days of constriction syndrome. And it's a syndrome where there's some process, some probably inflammatory process that affects cerebral arteries, causing, If you can see the picture below, causing segmental narrowing, there are areas and arteries that are just narrowed, and it leads to hemorrhage. Call our CBS And over the over a few weeks, people with our CBS almost always have recurring recurring thunderclap headaches. CT or MRI may show these little focal, um, subarachnoid hemorrhages. Here's one here, even smaller than the one I showed you in our previous slide and C T. A. C T angiogram, M R angiogram, conventional angio. They can all show segmental narrowing. They may miss it, but they usually show it. Cats can can, of course, like I said before Miss the hemorrhage or the radiologist may miss it. If we don't do something about this, they can keep happening. And it can be really serious, even leading to death. Um, uh, probably as a as a result of cerebral oedema over time. And the management is to control blood pressure and to control seizures and just stabilize the patient. And this tends to be, believe it or not, self limited. It looks a lot like and I'm sure this has occurred to a lot of you. It looks a lot like cerebral vasculitis, which shows segmental narrowing. You can see in this picture above segmental narrowing. This is the so called string of beads appearance of cerebral vasculitis. These bleed to and these can cause thunderclap headaches. So could our CBS be a kind of cerebral vasculitis? It could be, but a lot of the vasculitis features are not present with our CBS kinds of cerebral vasculitis. Includes systemic vascular titties like granny luminous Angie itis besets disease, probably arthritis, no dosa. And there's a just a cerebral um, Angie, it is called p a C N s. So primary. Angie itis of the CNS. Um and, um, it can be a manifestation also of systemic autoimmune disease. And let's not let's never forget that you can get a vascular tick state cerebral vascular tick, state secondary to viral and bacterial infections of various types generally involving the CNS. And I'm waiting to see reports of covid causing this presentation of vasculitis is generally kind of stroke, like with systemic symptoms and signs. Rashes are three colleges, of course, and all the gamut of collagen, vascular and inflammatory diseases. Or it can present just with the thunderclap headache as well as some neurologic deficits and, uh, seizures and so on. Here's a picture of primary Angie itis of the CNS, and you can see this string of means appearance, focal, segmental narrowing of arteries. How do we tell the difference? Well, R. C, B S and C CNS vasculitis are similar, but notice our CBS usually doesn't cause neurological deficits, which we see in vasculitis. Also, our CBS has generally normal CSF maybe a little yellow tinge like I showed you in that case before Little Santa chromium. But CSF and vasculitis is almost always pro tenacious. And what's the difference between our CBS and vasculitis and subarachnoid hemorrhage. By and large, the blood and subarachnoid hemorrhage comes out at such force that it fills a lot of those spaces that we were. I was showing you before. So the bleeding is diffused, whereas our CVS and CNS vasculitis a little more focal. So these focal little areas another disease called press post irreversible encephalopathy syndrome who could also get These folks can also get thunderclap headaches, and they can also have bleeding, although usually not bleeding. But they do get. They do get thunderclap headaches. And it's a very strange syndrome where in posterior regions of the brain, there is this white matter alteration, leading to headaches, confusion, seizures, vision, loss, even strokes. And it seems to occur in the setting of hypertension. So some sort of hypertensive situation, but also occasionally in people who take immunosuppressants in patients with renal disease and in Lupus. What's the management here? Also control blood pressure control seizures and some of the similarities have led us to notice that there's an overlap between the R. C. V s syndrome and this press syndrome, and you know you'll recognize these things if you've seen a few cases. But but they are very surprising. They can present with subtle things, like just headaches or a little bit of confusion. And we have to make the diagnosis quickly. Um, like I said, there's this overlap that we don't understand that well yet. And I listed some of the things that are common to both. And they may be actually on the same spectrum of these of these disorders that have maybe clinical similarities and path of physiology. So why do people get sudden headaches and subarachnoid hemorrhages and our CBS and press? Um, why do they What's going on? Why does that happen? Well, I remember. And you probably due to being taught that any blood in the subarachnoid space is irritating to the dura, just like meningitis. Being an inflammation around the Dora is painful because it irritates these meninges. Maybe that's possible. But, um, that may not be true at all. Maybe a myth. And maybe there's just an abrupt increase in intracranial pressure. Or there may be catacomb ian release due to blood causing a reaction. And interestingly, thunderclap headache does occur in physiological states of fio and sympathy, um, a medic drug toxicity. So it may be more of a home, a static, um, cause of headaches. Bearing that in mind, I bet you've seen patients with acute hypertensive crisis and even though that wasn't the biggest problem, but they can present with just headache and believe it or not, even in this day and age, people can report to the ER or urgent care center, and someone forgets to take a blood pressure. And that can go on. And it's obviously highly dangerous. A clue or fungus? Coptic abnormalities, as you see above disc swelling and hemorrhage is and the fund s et cetera. So let me get back to our cardinal case, this young guy with a sex related headache and that's what it is. It's this primary headache associated with sexual activity. We don't really know what causes it. Highly mysterious has a few features in common with migraine, but by and large it's different. It lasts from one minute to 24 hours in duration. It's usually pretty severe. It can last up to 72 hours with milder intensity. A lot of people get recurring sex, headaches, orgasmic headaches, coital headaches. Many different synonyms have migraine, and interestingly, you can prevent these if you're a person that gets sex related headaches, orgasmic headaches. If you take into medicine before sexual activity, it can prevent the headache. They can also be prevented, as can migraines with beta blockers. And these two approaches can be highly valuable to patients. As you can imagine, it becomes scary to think about having sex. Um, and of course, this doesn't just happen with intercourse. It can happen with any sexual activity. So one of the things that we think about when we classify headaches is what what What are similar are migraine and sex headaches. Similar are migraines and, um, tension type headaches. Similar are sex headaches, a kind of exertion? Headaches? Well, that was my first thought when I started seeing a lot of patients with sex related headaches. But apparently not because, as you can imagine, sex headaches, coital headaches can occur with very little exertion. And by the way, I mentioned this already, they can occur with any activity that leads to orgasm or close to orgasm. Um, exertion, headaches look a lot more like migraine, in fact, so not really the same as sex induced headaches, however, and here's a bothersome feature. Both exertion, headaches and sex related headaches respond to Indo medicine. Well, let's talk about meningitis, encephalitis, acute sinusitis. Things we think about frequently. Um, these headaches can cause thunderclap. These conditions can cause thunderclap headache. It's usually more gradual. So, usually encephalitis, sinusitis, meningitis. There's a There's a ramp up a ramp up of the head pain. Well, let's do another case. Is a 30 year old woman transferred to your hospital screaming in agony? I'm not kidding. Ah, it actually happened to me. I got a call from an ex resident. I was a residency program director, so I had a lot of X residence brown the where I was practicing, uh, in my institution and the ecology says I have a patient that I need to transfer you because she's screaming in agony and I said, No, that's not possible. People don't scream in agony with headaches, and he says, Yes, she is. And make a long story short, he transferred the patient. Um, and by the way, the cats can have been normal. Um, the only history that was of any interest was that number one. She had some air travel recently, and she had begun an oral contraceptive pill four weeks ago and she got to the ward and she was screaming, but she, uh, with some morphine, she was a little calmer. Uh, but she was kind of sleepy, and she was non focal. And the only reason I thought of the correct diagnosis is because we had a similar case and to make a long story short again, she on MRV anagram was missing a huge part of her superior sagittal Sinus, which is a vein huge cerebral vein. And those arrows are pointing to where we should be seeing a vein. And we just don't because it's filled with clot. The cerebral venous thrombosis occurs in people symptoms For unclear reasons, estrogen can be a positive factor. Um, sometimes they occur after flying, she had done both things, changed the birth control pill and had had air travel. Um, hyper co available States, of course, can cause this hugely painful and can be life threatening. Um, it presents as a just headache in some patients, 15 to 20%. But a lot of them become altered in terms of the level of consciousness. They can have people oedema. They can have seizures. They can die because of increased intracranial pressure. I've listed some of the risk factors that I didn't mention. And sadly, they one can go back in a lot of these cases and actually see a diagnostic sign earlier. There's something called the Delta sign, which I'll show you in a minute. This is, uh this is I believe this patient's cats can look at on the left. Um, this is, uh, without contrast. You see an area here next to the red arrow that looks white, and it should be less filled, a non contrast. And after contrast, there, there in, uh, several venous thrombosis, you should see, actually the clot that dies surrounding the clot. And indeed you do in this patient, it's called the Empty Delta sign, so cat scans can diagnosis. All right, let's get to the next case. Young woman hospitalized for preterm abdominal pain, complains of sudden, severe headache behind the eyes. She's having trouble cooperating, but she can't see very well. She has blurred vision, and when you actually get into it, it looks like she has tunnel vision and she can't really walk. She can't. She's very clumsy, and you start to worry and you probably all know where I'm going with this pituitary hemorrhage. It's thought to be due to the pituitary enlargement that increases that happens in pregnancy with increased vascular charity, and it can present with visual loss by temporal visual loss and some diplo. Pia sometimes, and this used to be thought of as 100% fatal. Luckily, it's not with good neurosurgical intervention. It's generally not fatal, but it needs to be diagnosed. Um, corticosteroids need to be replaced, surgical intervention as necessary, and I'm sure you're thinking about other interest. Cerebral hemorrhages is causing, um, thunderclap headache. And they do. They do. There's usually more. You know, there's usually a Hemi, Paris's or vision loss or or a taxi to, um, altered consciousness, nausea. And but we do see these from time to time. It's the thing we always worry about. Of course. Um, why do they get thunderclap headache again? This is probably direct pressure on the dura, but it might be increased intracranial pressure. As I think we're seeing in this picture, you're seeing loss of Cell C and and that generally indicates increased intracranial pressure. All right, here's a case of a 42 year old long distance truck driver who drove to a local ER because he got a headache. Sudden right frontal headache founded the normal on exam. Except for this toe sis that you can see on the right side. It's not. It's not striking toasts, but, you know, you've seen enough cases of toast this. You'll know it when you see it. And he had a spontaneous carotid dissection. And the arrows are pointing to a very thin area of internal carotid, which is due to a thrombosis dissected wall of his carotid artery and thrombosis narrowing the Lumen of the carrot. And the problem with these, of course, is that they can cause thrombosis in sight there with, um, artery to artery embolization and stroke. Um, sometimes they do Well, sometimes these things are just noted in retrospect. Oh, yeah, I remember a bad headache. And then on some imaging exams soon after, there's a There's a dissection scene. Um, headache is supposed to be, uh, it's a lateral, but not always. Strangely enough, Um, the C T. S are usually negative. LPs are, of course, negative. The only thing that's a good, really good test for this is a C, T or M R angiogram. I just wanted to share with you the strange fact that carotid artery pain can easily refer pain to the head. So here is a study also done by Raskin showing that irritation of the carotid artery commonly causes pain in the head in these different areas. He actually stimulated the carotid artery in people and ask them where it hurt. I won't go into all the details. All I can tell you is that this would not pass the C S f I R B at this point. And then finally, there's this primary thunderclap headache that is of unknown cause and is considered a primary headache and not do anything dangerous. Problem is, I wouldn't diagnose this until you've really ruled out everything. I just thought I'd mention the so called primary stabbing headache. These are not thunderclap headaches because they're just very, very brief. They go away after a second, but it's something to think about. When patients tell you about these things, there's an ice pick in case interview are too young to know what an ice pick looks like. All right, here is a case of a rapidly progressive headache and a patient after spinal surgery recovering after spinal surgery. Terrible. When he stands up better, he lies down quietly. And of course, it's intracranial hypotension. Uh, CSF fluid, CSF leak, spinal fluid leak. And people get these terrible headaches when they stand up and it can seem like a thunderclap headache. I'm going to skip through this slide. I just wanted to show you a couple of pictures. Uh, that help us know when someone has a separate. Excuse me. Someone has a dural, uh, leak of spinal fluid. And one of them is this brain sag, also known as the Chiari Malformation subdural collections of fluid and dural enhancement. After, um, gadolinium is infused and just to keep on our sex theme, uh, intracranial hypotension. So CSF leak can actually be precipitated by sex causing a leak due to the exertion. Supposedly something called the crash migraine, which is the sudden migraine. And the term was invented by C. Miller Fisher. That's all I want to tell you about it. And I did tell you that Sinus sinusitis can is generally a more gradual headache, but occasionally, um, sinusitis can cause a sudden headache. Probably because of things shifting around. The clues are obvious fever, discharge and so on. I think this is my last case. I know I've been throwing a lot of cases at you, but this is what we like. And I thought I'd I'd I'd share with you. A lot of I've had the good fortune to be to have seen lots of cases of thunderclap headache. So I'm I'm sort of happy to share my share. My differential with you. Um, this is 66 year old man with hypertension and diabetes. I started having thunderclap headaches earlier this week, and he's in the ER only because his wife made him come. And some of the headaches are accompanied by John Shoulder pain. The pain is really bad. It can make him feel breathless. So what happened to this guy? Well, e k g was done showing key waves and pretty massive s t elevation in a pattern called a lot of you know about this e k g tomb Spalding, because it's thought to be a pretty dangerous condition diagnosis with a steamy and cardiac septal algae. And I kid you not acute cardiac ischemia can cause a headache we still don't understand the referral pattern, but we've seen this time and time again, so headaches can herald this. And I don't mean to rev up your anxiety about people with headaches, sudden headaches, but something something to think about. It's just a slide showing a colloids system the third ventricle. It's a famous cause of thunderclap headache, but it almost has never seen. I've never seen a case of it. I'm probably never will, but I wanted to be complete. I also wanted to be complete and showing this entity. It's a sudden, explosive feeling in your head called the Exploding Head Syndrome. It really doesn't hurt. It's just a feeling that there's an explosion and it's considered a sleep disorder. So I'm going to move through in the interest of time and just show you a, um, a kind of a heuristic for how to approach these multi, uh, types of thunderclap headache. I'm gonna I'm gonna skip through that. Here's a Here's the heuristic. Um, I'm not asking to memorize this. I just wanted to show you that people have made up all sorts of heuristics and here is mine. Person comes into the ER or urgent care with a sudden bad headache. CAT scan If the CAT scans Negative LP, including Spectra Fatima Tree, to look for his anthro mia if it's in the six hour to one week time frame. If it's not, If the headache happened just an hour ago, you might as well not bother doing spectral Tom a tree. If the LPs negative or you're not sure you may be hit a vein and you're just not sure, then cat scan angiogram or M R angiogram to rule out aneurysm, as well as our CBS vasculitis press and cerebral venous thrombosis. You've done all that, then you really finished your work up. But do keep other causes in mind, like cardiac septal algebra infections and some home a static, you know, uh, condition. So I'm ready to conclude as you gathered from my, uh comments today, there are lots of causes of thunderclap headache. I'm sorry about that. It's worth making a note card for yourself or, you know, a virtual note cards somewhere to think about these things, some of which need to be diagnosed right away. Some are benign, but some of which really need to be, uh, considered right away. Diagnostic image is imaging is usually necessary. And just keep in mind this broad, uh, d d x. And, uh, I'll finish by saying thank you to all my patients in college, at the use and colleagues colleagues at the CSF Headache Center and thank you all for listening.
