DIFFERENTIAL DIAGNOSIS OF HEADACHE IN EDS (Transcript)

Transcription

1 The Ehlers-Danlos Society P.O. Box Montgomery Village, MD USA Phone: The Ehlers-Danlos Society - Europe Office Ludgate Hill London EC4M 7JN UK Phone: ehlers-danlos.com info@ehlers-danlos.com DIFFERENTIAL DIAGNOSIS OF HEADACHE IN EDS (Transcript) 2017 EDS Global Learning Conference September 9, 2017 Fraser Henderson, Sr., MD Video

2 2 F. Henderson Alright. Thanks very much, Lara. It was a wonderful dinner last night and very heartwarming. It s a wonderful group of people. I m very honored to be here today. I m going to talk about headaches, which is rather like opening Pandora s box, but we ll do our best. When I see someone with headaches I think of all of these things and actually a lot more, and we re going to discuss them today. Start off with Chiari and this is a typical Chiari malformation and you can see the cerebellum here, dipping through the base of the skull, the foramen magnum and here s the syringomyelia. So this is the Chiari malformation right here, dipping through the foramen magnum and that is a classic Chiari malformation with a syringomyelia right here. That is likely to cause headaches, but chronic migraine headaches occur three times more commonly with Chiari malformation. They can be variable migraines, tension-type headaches, cough headaches. And so, the presence of a Chiari doesn t necessarily confer a diagnosis of a Chiari headache. The Chiari headache is typically characterized by the fact that it s precipitated by a cough or a Valsalva maneuver. It may be protracted from hours to days, usually in the suboccipital region, or the back of the head. And it s often associated with signs of cerebellar symptoms such as incoordination and nystagmus, or lower brainstem or spinal cord changes. Well, here s a patient for whom I had performed a Chiari decompression a number of years before, and I had decompressed the foramen magnum here, and now she came back with severe headaches and some memory changes and fatigue. So, one could look at this and say, This person really needs another decompression. But, I obtained a CT scan and you can see on the upper left there that the brain looks very tight. I obtained a MRI and if you look at the MRI on the lower left, you ll see this increased blood flow along the perivertebral venous plexus. I obtained a MRV of the brain, a venogram, and you can see that the blood flow through the saggital sinus there with the arrow is not flowing. That s a blood clot, a thrombus. She had a thrombosis of the sinus, the major draining vein from the brain, and if you look on the arrow there, the left transverse sinus shows no flow. We treated her with Lovenox and within a couple of weeks we had good flow through the sinuses and she improved. Now, this young lady had undergone a craniocervical decompression one year before, and she is now experiencing global headaches that were increasing over several days. She had leg weakness and incontinence, and we thought, Well, maybe this is tethered cord. And then she had a personality change and memory loss. That made us think of the superior sagittal sinus and, indeed, we performed a venogram and found, again, a thrombosis in the sinus and we treated that with Lovenox and she was out of the hospital a week later. This 25-year-old girl with severe retro-orbital

3 3 pain, pain behind the eyes, and global headaches, also had dystonic seizures. Then she developed a loss of consciousness and we thought we were losing her. The MRV showed a total thrombosis of the left transverse sinus seen here and we treated her with Lovenox and she literally walked out of the hospital, walked out of the intensive care unit two days later. Dr. Liu down at the University of Virginia- he s now moving up to Hershey in Pennsylvania. He s one of the leaders in this field and I asked him what he felt were the characteristic signatures of thrombosis in the brain, and he said moderate-tosevere headache. The patients complain that, My eyeballs feel like they re popping out. There s a pressure in the head pushing outward. The pain may be present upon awakening, sometimes decreases with standing up, but can also worsen as the day progresses. If there s a thrombosis in the superior sagittal sinus, that s the sinus over the top of the head, there are usually stroke-like changes, cognitive changes, and it s more serious. A lot of patients also have pulse-synchronous tinnitus, meaning there s a pulsatile ringing in the ears with every heartbeat. Now, thrombosis can occur in the jugular veins as well. On the left you see a normal jugular vein draining the blood out of the brain, and on the right, you can see the jugular is pinched by the transverse process of the first cervical vertebra and other structures. Now, we re finding out in the last few years, that all of the blood does not drain out of the brain through the jugulars. In fact, when you re standing up, a lot of the venous drainage occurs around the spine, the perivertebral venous plexus, and when you lie down, most of the venous drainage is through the jugular veins. Now, if you look at a standard CT angiogram, a CT with contrast, on normal people a quarter to a third of them will have some degree of jugular venous compression. It s not that easy to make the diagnosis. The compression is usually by the posterior belly of the digastric or the hilar ligament, often over the transverse process of C1. But about one in five patients have a severe stenosis and half of those have collaterals around the base of the skull, around the condylar veins as shown here. Now, just last week I saw a lady who was complaining of continued headache and brain fog and I think we had ruled out issues in the brain itself and the cervical spine, so I did a lumbar puncture. Pressure was moderately elevated. Her vision got better but the headache continued. We obtained this MRV and it shows that the blood is draining through the transverse sinuses, but then instead of draining down the jugular veins, it s going through all of these other facial and perivertebral veins. She

4 4 had a bilateral jugular venous thrombosis or occlusion. And that s one way that the jugular vein is treated with a stent, and Dr. Liu performed that procedure. This 57-year-old man had a sudden pain in his left eye and double vision and then the following day, weakness on that side of the face. He had normal retina, normal fundal exam, but he had weakness of the left eye muscles, a drooping left eyelid, a sluggish pupillary reflex, and very high intraocular pressures. And this is typical of a carotid or a cavernous malformation occurring in an EDS vascular type patient. Typically, there ll be a bulging of the eye, weakness of the muscles, and an afferent pupillary defect with very high intraocular pressures. This gentleman presented with the new onset of suboccipital pain on one side and decreased vision. We performed the CT angiogram and you can see that the vertebral artery is not flowing at the C2 level on the right side. And remember, the radiologists do everything backwards so that when I say right, it ll look on the left to you on the film. The arrow shows a no-flow through the vertebral artery. And on these axial views, which are slices through the spine, you ll see no flow on that side. This is characteristic of a vertebral artery dissection, with suboccipital headache on the side of the dissection, altered vision, dysarthria, which is difficulty speaking, impaired coordination, stroke-like symptoms. It usually occurs after blunt trauma, manipulation, even massage, and more often than not in the hypermobility/connective tissue population. And now with its counterpart, dissection of the carotid artery, these two arteries account for one-fifth of non-hemorrhagic strokes. The pathophysiology of what s happening is that blood is breaking through the inner lining of the artery and going into the wall of the artery and occluding the flow through the artery. That s a dissection. The blood dissects into the wall of the artery. Here s a normal vertebral artery on the left, and on the right, you can see kinking of the vertebral artery, and this person had just very vague symptoms of TIA-like symptoms. This young lady from Canada had her entire left cerebral blood flow coming from the right side through an unusual branch from the internal carotid artery, and she had TIA-like symptoms. And there s that unusual branch coming from the right side to feed the left. This 35-year-old woman with Ehlers-Danlos hypermobile type had a 20-year history of severe bifrontal headaches and emesis. It just happened that the week before she went to Hopkins and had a full vascular exam and was given an A-OK. But on this morning she came into the emergency room. She had been massaging her sternocleidomastoid muscles vigorously the night before and now had this extreme

5 5 headache. It was like an aneurysm. So we got a CT scan, which was normal, and so I did a CT angiogram and we found a dissection of the left carotid artery. So there s no flow coming up the left carotid. She should have had a stroke. But then, it turned out she also had a dissection on the right side and she should have not survived, but she did with almost zero neurologic deficit. Now, if you have a carotid dissection, typically, there is pain over the temple, over the side of the head. There is often a loss of vision or decreased vision on that side. There may be a small pupil, miosis. It s part of a syndrome called Horner syndrome, which is ptosis, miosis, anhidrosis. Now, we re back to her Chiari again very easy to assume too little looking at this Chiari. Say, Well, right. I m going to decompress that and the headaches will go away. But ligamentous laxity confounds a number of these cases. The literature shows that there s a failure rate of decompression for Chiari that ranges from 20 to 50% depending what series you look at. Now, on the right there you see the decompression of the Chiari. That itself may not take away the headache. Jörg Klekamp looked at 45 revision decompressions and found that over 20% needed a reduction/ fusion/stabilization for signs of instability or basilar invagination. So he stressed the importance of dynamic studies to look for instability and to do a fusion if necessary. Milhorat and Paolo Bolognese and Clair Francomano and others showed in a very large series that at least 13% of Chiari patients have a connective tissue disorder. I think that that rate is much higher, at least in the patients I ve seen. But keep in mind, if you have EDS you can have Chiari symptoms without having the Chiari. Dr. Castori has done a great deal of work with EDS and we re very indebted to him and he s documented the severity of headaches of EDS patients. Jacome has noted the hypothesis that Chiari malformation is a consequence of occipitoatlantoaxial instability, may be more common in symptomatic EDS patients is supported by the reports of EDS cases with headache and a Chiari malformation. It s not hard to understand why hypermobility should cause headaches when we recognize that the stabilizing structures between the cranium and the spine are ligamentous, primarily. There are muscles, shown there in red, but the major stabilizing structures are ligamentous. That s the condylar ligaments, the tectorial membranes. Goel has done a great deal of work in India and he ask the question, Why does ligamentous instability give rise to basilar invagination? And he says that instability gives rise to micro trauma and this causes a kind of resonating pathophysiological process where the trauma causes more neurological injury: less control over the head, less neuromuscular control, and then increasing instability. This is exacerbated by malnutrition, vitamin deficiencies, and deconditioning, which is what we see in Ehlers-

6 6 Danlos syndrome. Now, Dr. Grahame and others noted for the last 20 or 30 years that headaches and quadriparesis and clumsiness suggested that something was going on, not in the joints, but in the central nervous system. Anne de Paepe, who is Fransiska Malfait s mentor, showed in this patient with EDS, the basilar invagination, the compression of the brainstem by the odontoid. I think you can see that significant compression right there. That s basilar invagination. Now, Doug Brockmeyer out in Utah showed in his retrospective series of over 100 patients that more than 20% needed an occipital cervical fusion, usually for basilar invagination or a kyphotic clivo-axial angle. So when does ligamentous laxity at the craniocervical junction become pathological? Probably every EDS patient has some of degree of hypermobility at the craniocervical junction, but when does is become pathological? On the lower left, that s a patient with rheumatoid arthritis and the odontoid is sticking up into the brainstem, and that s clearly pathological. The second and third cases you can see a retroflexed odontoid compressing the brainstem. We had a meeting in San Francisco in 2013 and representatives from 17 institutions agreed that there were three useful radiological metrics that would guide us to the formulation of whether that patient had instability or basilar invagination. We ll go through them. First is the clivo-axial angle, and that s the angle between the base of the skull and the back of the second cervical vertebrae. On the left, that s normal about 150 degrees. On the right, that s clearly pathological. That angle is actually 120 degrees and anything less than 135 is probably abnormal. The kyphosis of this angle between the base of the skull and the spine is what causes a kink in the brainstem, and if you kink the brainstem it doesn t work properly. Keep in mind that the brainstem is wired into every part of the cortex. [Inaudible] happens on the surface of the brain, it does not relay it through the brainstem and, actually, the cerebellum for that matter. A Grabb- Oakes measurement published in 1999 in Alabama looks at this line drawn between the skull base, the basion and the lower end of the C2 vertebra. Here s the basion and here s the back of the C2 vertebra, and the measurement from that line out to the dura should be, normally, about 5 to 6 millimeters. If it s 9 millimeters or more, then there s a high risk for ventral brainstem compression. And on the right there you ll see more than 9 millimeters, and that represents ventral brainstem compression. Harris looked at 400 subjects and he found that the distance from the basion, the base of the skull, to the top of the odontoid, was always less than 12 millimeters and said if you had that distance, 12 millimeters or more, you had craniocervical instability. Furthermore, that measurement should not change from flexion to extension. It

7 7 should remain constant. Here s a normal the person is bending forward and the basion is lying right above the middle of the odontoid, and on extension, it s still there. That s normal. But here s an abnormal case. Look at that odontoid and the posterior axial line is 15 millimeters away from the skull base. That s clearly very abnormal. Here s another abnormal case, in flexion on the left you see the base of the odontoid is about 7 millimeters from the posterior axial line, and on the right, the skull slides back. It s translating and there s abundant literature that shows if the translation is more than 1 or 2 millimeters, then you have craniocervical instability. Now, if you don t have dynamic imaging you might miss this. On the left, that s a normal supine view with the patient lying on his back, and you can see, well, there is a little bit of basilar invagination but it doesn t look too bad. The brainstem is pretty straight. But on the right, you can see that the skull has shifted forward and is now a more ventral brainstem compression. So how does a patient with craniocervical instability present in terms of headache? The headache is in the suboccipital region, 70% also have neck pain. The pain can sometimes radiate to all parts of the cranium and is described as shooting, throbbing, stabbing, sharp and it s worse with bending, exertion, and looking up. So what s the effect of treating this with a reduction? A reduction is simply reducing the deformity and a fusion with bone, usually allograph from the bone bank, and stabilization with screws into the bones. That s a fusion stabilization. Well, we looked at this at one year and now we re looking at five-year data, but conservatively, before surgery, these patients had an average pain of 8.2 and it dropped to 4.5 on average. Notice the pain. There s still pain there and that s because most of these patients have several types of headache. They may have TMJ pain. They may have migraines. The pain does not go away with the craniocervical fusion, but it does improve, and similarly with neck pain. I ve been discussing guidelines, like the pirate said, they re guidelines, not rules. So this lady clearly has a Chiari malformation and has even a stretching of the brainstem and a kyphotic clivo-axial angle, which her headache was quite tolerable. Her neurologic deficits were minimal and she s still working, so I advised her not to have surgery and we ll just follow her year-to-year. Here s a young man who played the French horn and you can see in the left the Chiari, the cerebellum pushing through the foramen magnum and there s something unusual about the bones there. On the CT scan, if you look on the right you see that the first cervical vertebra is fused to the skull base. So this turned out to be a Hox D3 homeotic transformation. And I know all of you all were thinking that when I showed you that picture. So I performed a decompression on him with the idea that he may- will probably need a stabilization in the future. But this is his case at one year and he has

8 8 great CSF flow and he seems to have maintained his stability between C1 and C2 and not needed any further surgery. Now, many people assume that headaches originate, as well as reside, in the head. But Dr. Long, the former chairman at Johns Hopkins, has emphasized that a lot these headaches begin in the neck. To quote him, he says, We all understand sleep disturbances, visual disturbances, dysautonomia associated with Chiari. But headaches, less well-understood. At least 25% of patients after Chiari malformation surgery continue to have the headache. This headache, he states, is clearly related to upper cervical instability. I simply want to re-emphasize that mechanical instability is well-known to occur as part of the normal pain process. He looks back to Kirkaldy- Willis, who was the first one to describe headaches as a result of spinal instability in His student, Harry Farfan, described microinstability as causing pain. And then [inaudible] described ligamentous laxity as a cause of headache. Long has, again, made the point that acute strains and sprains of ligaments, which are impossible to diagnose on any imaging we have, can cause headaches. Cervicogenic headache: that s a headache that arises in the cervical spine. It is one of the lesser causes of headache in the general population, but has the highest quality of life burden, two-thirds of the population of headaches, of which half are misdiagnosed. Tension headaches have a prevalence of 38%. Migraine prevalence 10%. Chronic daily headache 3%. Cervicogenic headaches, typically about 3% of the total in the normal population. But cervicogenic headaches can also arise as a neuromuscular phenomenon. Typically any structure innervated these manuscripts said in the upper three cervical vertebra are a potential source of headache. But I can tell you that persons with spinal instability all the way down to C6-7, or even C7-T1 can have headaches. The headache just travels right up the spine. And at C6-7 it can interfere with the vertebral artery, which enters at that level, and stimulation of the vertebral can cause a severe suboccipital headache. Muscle tightness involves at least one out of three cervicogenic headaches and typically involves the trapezius, sternocleidomastoid, scalene, levator scapulae, pectoralis, and major and minor short occipital extensors. Dr. Mitakides has talked a lot about this. The importance of those muscles and headache and how temporomandibular joint syndrome can actually trigger those muscles into spasm and cause headaches and sleep apnea and even weakness of the abductors of the arms. Now, C1-2 instability is really difficult to diagnose. It s been diagnosed in a it was found to be very common in the EDS vascular population. The mean rotation of the C1 upon C2 is about 35 degrees. And it s held in check by certain ligaments called

9 9 the alar ligaments that go between the skull and the odontoid I process. Now, if the alar ligament is compromised, this allows increased turning to the opposite side. So the distinguished Canadian neurosurgeon Harold Hoffman said that overstretching or rupture of the alar ligaments can result in rotary hypermobility or instability. When I make this diagnosis I look for headache and neck pain, syncope, either blacking out or pre-syncope, nausea, tenderness over C1, spasticity, hyperreflexia, sensory deficit to pinprick, which some of you have experienced, and excessive rotation of C1 upon C2. Now to look for this I put the patient supine on the CT scanner, and then they rotate their head fully to left 90 degrees if possible, and then fully to the right. The scan is from the skull base down to C3. And if the angle- if the measured angle in the top middle between the first and second vertebra is more than about 41 degrees, then they re in the range for C1-2 instability. And you can see lower left how with instability, the facet overlap; those facets should be overlapping, but they re sliding off one another and if you just tilted this girl a little bit more in that direction, she might dislocate that neck. At a 45 degree angulation between C1 and C2, the blood flow through the vertebral arteries ceases. And that s the blood flow to the brainstem and the back of the brain, the visual centers. Now we have a number of other ways to look at C1 and C2 instability, but it s still very difficult. Professor Smith in Great Britain has done excellent work in conjunction with Dr. Grahame, and on the upper left here you can see the, in black that black band, that s the transverse ligament that holds the odontoid in place, and on the right that transverse ligament is very sketchy. That black line, that person has instability. If you look upper left, above that white area is a black band. That is the alar ligament and looking down lower-left you can see thinness of that ligament, and that s an unstable alar ligament. Here s a patient who had an eccentric odontoid within the C1 ring. You see it s tilting over there, and that s probably got an alar ligament incompetence. This patient had a transverse ligament incompetence, shown here on the left, and on the middle picture, middle MRI, you can see that the cord is being squashed between the odontoid and the posterior ring of C1. Now, Goel has described a fairly normal-looking appearance on MRIs, but intraoperatively C1 and C2 can be unstable. It turns out, looking at the pictures that he showed in his manuscript, that this patient, shown with the arrow, actually had a Hox D3 homeotic transformation where the C1 ring was fused to the skull base, which puts a lot of stress between C1 and C2, and that s why that patient was unstable. Yin, Yu, and Zhou from China reported on other patients where the C1 slides posteriorly off C2. Here s an incomplete C1 ring that can increase the instability of C1. This is how we fix it.

10 10 We place a bone graph between the ring of C1 and C2, shown here. That s the sagittal view from the side, and upper right you see the view from the back. And then the 3D reconstructions down below, and the you might make out the hardware, the screws on the side and the bone graft in between. This is a Kimmerle anomaly. It s that circle of bone above C1 due to the calcification of the fibrous ligament of the condyle. It entraps the vertebral artery. This is common, but sometimes it may cause deafness, dizziness, or drop attacks, or paresthesias, or even dissection of the vertebral artery. It s very important to get dynamic films of the cervical spine if you suspect a problem there. This young lady had a relatively normal supine MRI on the left, but when we placed her on extension on the right, you can see that there s spinal cord compression. This was discussed by Dr. Benzel, who is the chairman at Cleveland Clinic with Sadid, who pointed out that with a kyphosis, shown there on the right, there is a bending of the spinal cord and this can cause a sagittal bowstring-like tethering and a myelopathy. So you can see that the spinal cord on the left is actually stretched. On the right, it s the same patient, and that stretching of the cord causes myelopathy or injury to the spinal cord. Punjabi and White looked at all the criteria that make by which one would predict instability and a positive stretch sign such as flexing the neck, angulation on flexion and extension of more than 20 degrees, or a single angulation on 1 film of 11 degrees or more, a subluxation of more than 3.5 millimeters, the presence of spinal cord injuries, stenosis, radiculopathy, and so on. This lady had a headache, suboccipital pain, pain over the shoulders between the shoulder blades. We couldn t work out what the problem was. She had myelopathy, severe pain, and we obtained a flexion/ extension view, and on that extension view shown there you can see a subluxation of spine, compression of the spinal cord, and we fixed that with a simple anterior cervical diskectomy, fusion, and plating, and she left in two days. It may become difficult to differentiate between migraine and cervicogenic headache. Classically, in the non-eds population, migraines occur in the younger female population. They re in the front of the head, more often unilateral with nausea, phonophobia, noises sound too loud, photophobia, they re too sensitive to light, pain bending forward, relief with migraine meds, throbbing versus cervicogenic headache, more common in the males, posterior head, more often unilateral without nausea and photophobia. Pain is increased with neck posture and without the throbbing. Unfortunately, in the EDS population, there s a lot of blurring of this distinction. The headache may arise from injury to the nerve fibers. You can cut a nerve fiber and then you ll get a neurological deficit, and that s very easy to diagnose. If the peripheral

11 11 nerve gets stretched or sensitized it becomes very difficult to diagnose. You can have a peripheral sensitization, or you can get sensitization in the brain and then you get paresthesias, which are annoying numbness in the hands and body, allodynia, which is a pain that seems to have no reference to the way you re causing a stimulus, dysesthesia, which is a painful sensation, hyperalgesia, which is hypersensitivity. These kinds of sensitization phenomenon are more difficult to diagnose through a standard neurological exam. Characteristic of that are the greater occipital nerve, lesser and third occipital nerves, which can cause very painful neuralgias. The posterior branch of the occipital nerve comes off the C2 nerve root, can be very painful. That arises from the C2 dorsal ramus and a small contribution from the third cervical vertebra. This is an ultrasound. That nerve rises up through the semispinalis capitis, the spinous, and the trapezius muscles, and then comes to lie about 1.5 to 2 centimeters off the midline at the back of the head. You can test these with a nerve block, but they can cause very severe pain. I m going to just go forward a little bit. Now, migraine headaches can also be triggered by a hole in the heart. This young lady was having TIA-like symptoms and migrainoustype headaches. We did an ultrasound with a bubble technique. We saw bubbles going from the right heart to the left heart and we knew there was a hole between the atria, and she underwent a procedure to correct that and the TIA-like and headaches improved. There are remote causes of headaches. Tumors can cause released proteins in the spinal fluid causing hydrocephalus. Tumors can also put traction on the spinal cord, causing a tethering effect that can cause headaches. I had one lady, shown there on the right, with this huge ependymoma and terrible headaches. When I took out the ependymoma her headaches went away. That s an occult just like occult tethered cord syndrome. If the spinal cord is tethered by a tight filum, that s the little fibrous band that holds the spinal cord down to the base of the spine. That can cause headaches. We found that about half of our patients with tethered cord have headaches and it feels like something pulling on the back of the head. It s worse when they flex their neck downward. TMJ dysfunction is a really common cause of headaches and neck pain. This is a major, major issue with Ehlers-Danlos syndrome. This is a very highly sensitized structure on the side of the face, right here. I was sitting next to one of the world champion boxers on the flight up, and he was talking about the knockout punch hitting the jaw, and I suggested that instead, hit back over the TMJ but make sure you don t kill them. Anyways, he s going to get back to me. I m going to read his MRI for free. It s highly innervated and it relates to a lot of the muscles in the neck. It can cause dysphagia,

12 12 sleep apnea, weakness, and headaches, severe headaches that wake you up in the middle of the night. So I encourage you to see people of caliber like Dr. Mitakides, who is one of the best in North America. There s some others like Joe Tregaskes in Richmond. It typically refers pain to the suboccipital region, can refer pain into the levator scapulae and cause pain under the shoulder plain, pain over the temporalis muscle, and pain above the eyes. It s worsened with chewing, talking, and wearing a neck brace. A lot of patients who have craniocervical surgery can wear a brace. The brace will cause more TMJ pain and then it becomes a real problem. The disorders of immunity, and Anne Maitland has given a brilliant discussion of those, so I won t reiterate mast cell activation syndrome, which is exceedingly important. We have cases with PANDAS, which is pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections. They cause headaches and movement disorders and compulsive behavior. There are other forms of antibodies to the various neural receptors in the brain and spinal cord that can cause a brain on fire and all kinds of neurologic deterioration, such as the anti-n-methyl-d-aspartate receptor encephalitis, which is characteristic of the whole group of paraneoplastic limbic encephalitis. So it s really important then to make a precise diagnosis and one of the important things here is the dynamic flexion/extension MRI of the cervical spine, sometimes of the thoracic and lumbar spine, and all of the other tools that we use. In conclusion, though a useful measure of disability and suffering, headaches are highly variable and nonspecific. A precise diagnosis must be predicated upon a substrate of demonstrable neurological and radiological findings. Awareness of the many comorbid conditions of Chiari malformation is important to establish the origin of the headache. Ligamentous laxity seems to be an important feature in many of the conditions that generate the headaches. So awareness of the diagnostic features of hereditary collagen disorders assists in the recognition of these and I don t need to tell this group that. I d like to acknowledge my coworkers: Clair Francomano, Myles Koby, Peter Rowe, Rodney Grahame, Alan Pocinki, Petra Klinge, Ed Vandersall, Mark Luciano, and Mark Alexander, Jonah Murdoch, Jessica Adcock, Rebecca Tuchmann, [Inaudible] Wong, and Michael Healy in preparing this talk, and also Joe [Inaudible]. Thank you for your attention. Transcription by Christina Cole