Slides
Transcript
Thank you very much for the invitation. Although I’m not really sure what I did to deserve this topic, but I will do my best. I have no disclosures. What we’re talking about here in this topic is this category out of the classification that we know, and I’ll talk a little bit about the simple cysts but also the more complex dural ectasia.
For the nerve root cysts we’ll usually call them Tarlov cysts, first described in 1938 by a Canadian neurosurgeon, and then in the 80s a more detailed classification talking about whether there’s nerve root fibers in the cyst or not. I’m not sure that’s particularly useful, but at least something to work with. There are different types of cysts. Whether it’s the dura that encloses the cyst, or whether it’s arachnoid that’s herniating out, are probably different types of cysts.
Pathologically, though, the typical Tarlov cyst is a cyst where between the dorsal ganglion and the dorsal root and the ganglion between the perineurium, which is the arachnoid, and the endoneurium, which is the pia over the nerve. Most common in the sacral part of the spine but can be elsewhere. And the pathogenesis is really not clear. There are a few theories about how they might form, but still I think unknown. They’re pretty common. About 5 to 10% of the population have them, more common in women and more common in older age. Presumably they form during age.
They are associated with intracranial hypertension, and in about 4%—and it’s probably higher than that—I think SIH patients have nerve root cysts. So if you think about Tarlov cysts apart from SIH, they can be symptomatic. They can cause nerve root pain. Neurosurgeons were always taught that Tarlov cysts are incidental findings, but they can be symptomatic. They can cause pain in the bone or the periosteum of the bone where they form, they can weaken the bone and cause fractures, and they can be so large and go into other spaces such as the pelvic cavity and cause problems there. They never get smaller, but they sometimes get bigger, and when they get bigger that is associated with the onset of intracranial hypotension.
Tarlov cysts can be treated directly, most commonly I think directly injected with fibrin glue, and there are varied types of surgical techniques to treat them. It can be difficult, I think, to tell the difference between the typical Tarlov cyst and the nerve root meningeal diverticulum that we’ve been talking about as part of the syndrome of SIH.
This is a person who I think these are Tarlov cysts but presents with intracranial hypotension. She has no history of connective tissue disorder. Tarlov cysts, or nerve root cysts, are often the basis for CSF-venous fistula. So it can be a Tarlov cyst that is the responsible lesion for intracranial hypotension because of a fistula.
But there also can be the basis for a diverticulum. This is a patient with multiple nerve root cysts, and hopefully you can appreciate that the morphology of that is different and that is likely to be an arachnoid diverticulum out of the nerve root sleeve. Marcel, this is a nerve cyst — arachnoid diverticulum coming out of the nerve root cyst. The difference from the typical Tarlov cyst, of course, apart from the ones where there is a CSF-venous fistula, is that there is usually CSF in the epidural space—usually paraspinal CSF. So that is an indication that it’s a diverticulum rather than just a typical Tarlov cyst.
Now coming to dural ectasia. The definition of that is widening or enlargement of the whole dural sac, most commonly lumbosacral. It is probably a pressure-driven phenomenon of increase in size of the dural sac. So with upright posture, there’s higher pressure in the sacrum and lumbar spine, so that’s where they most commonly occur. It’s probable that there is a weak dura and/or high CSF pressure that drives the formation of dural ectasia.
Probably most well recognized in Marfan syndrome—about two-thirds of Marfan patients will have dural ectasia. Loeys-Dietz, Ehlers-Danlos, particularly the hypermobile type, neurofibromatosis type 1, ankylosing spondylitis. And sometimes, as in the patient I showed you earlier, there’s no underlying known connective tissue disorder. There’s no definite evidence in the literature, but I think it’s pretty clear that Tarlov cysts, or at least nerve root cysts, are more common in patients with otherwise dural ectasia.
But how does dural ectasia cause SIH? Well, it could be, as we’ve heard, this change in compliance so that the weakened and enlarged dura—that big CSF pool—can enlarge more easily with upright posture. Or it could be that there is an actual leak. These patients of course will often have a connective tissue disorder, and there might be a dural tear, particularly type 1 tear. They’re more prone to developing meningeal diverticula from the nerve root cysts, so it could be type 2. Or it could be that there is a Tarlov cyst, as I showed, connecting to a CSF-venous fistula.
Sometimes it’s not clear, and sometimes these patients present with, as in this case, superficial siderosis. This is one of my patients with NF1, with no evidence of CSF leak, no symptoms of intracranial hypotension, no orthostatic headache, but presents with features of superficial siderosis with deafness and ataxia.
So how does this happen in dural ectasia? Well, that’s not really clear. Is it that just because there is low pressure the intradural vessels are more fragile and more prone to bleeding? There’s no definite evidence for that. Is it that there is a dural tear with CSF leak and blood is entering through that dural tear, but in cases like this there’s no evidence for that? Or is it just because the patients have a connective tissue disorder, disorders of collagen and elastin, that the vessels are more likely to bleed? I don’t think we really know.
So I’ll talk a little bit about each of the common types. Marfan syndrome is a genetic disorder. It’s a relatively common genetic disorder, one in 5,000 to 10,000 people. And it’s a mutation—different types—but a mutation in the fibrillin gene, and fibrillin is an extracellular matrix protein. So with an abnormal extracellular matrix the tissue strength is reduced. But also fibrillin sequesters transforming growth factor beta, and transforming growth factor beta is increased then in Marfan patients because it’s not sequestered. Transforming growth factor beta actually degrades collagen and elastin.
So there’s this double hit with Marfan syndrome in the extracellular matrix. It’s an autosomal dominant disorder, although about 25% of them are a spontaneous genetic mutation. It’s a multi-system disorder. Although we’re focusing here on dural ectasia, they have many other system problems.
Here’s an example of Marfan syndrome: typical ectasia, dural enlargement in the lumbar and sacral spine, but with associated nerve root cysts as well as the overall dural ectasia.
Loeys-Dietz is actually thin and typically pretty similar, quite a different genetic condition though, relatively recently recognized, and the incidence is not very well described. It’s a mutation of the transforming growth factor genes. There are multiple different types that lead to abnormal collagen. So it has the same kind of extracellular matrix underpinning as Marfan syndrome. And so it has very similar phenotypic presentation, although there are some differences: hypertelorism and different skin abnormalities.
Ehlers-Danlos is a fairly heterogeneous condition with multiple genetic abnormalities that can lead to that phenotype. The hypermobile type is the most common, about one in 5,000 people. It has abnormality of collagen and another extracellular matrix protein, tenascin-X. So again, similar to the Marfan and Loeys-Dietz syndrome where there’s an extracellular matrix underpinning to the connective tissue disorder. Depending on the type, it can be autosomal dominant or recessive, and in the hypermobile type they also have craniocervical instability, mast cell activation, and of course POTS. And with the craniocervical instability and POTS, the symptomatology can be quite similar to SIH, so it can be very difficult in these patients to tease out what the underpinning problem is.
With NF1 it’s a little bit different. This is a mutation of neurofibromin, which is an intracellular protein. So this is not an extracellular matrix protein problem. The protein here is a tumor suppressor protein. It regulates the RAS and MAP kinase pathways, usually autosomal dominant. How does it cause dural ectasia? It’s not a connective tissue disorder in the sense that the other conditions are. There’s not an abnormality of extracellular matrix.There is a theory that it’s infiltration of the dura by plexiform neurofibroma, but my experience is that that’s not really likely. The dura is very thin and doesn’t seem to have what would be considered infiltration with tumor. And in the NF1 sacral enlargement in my experience at least is less common and suggests it’s perhaps a different underlying etiology.
This is that patient with neurofibromatosis type 1 presenting with superficial siderosis, and as I said it’s not sacral. I gotta mention that ankylosing spondylitis is also associated with dural ectasia. How that happens is really unknown. The actual etiology of this condition is not well understood. It’s probably an autoimmune disorder. It is associated with a genetic HLA-B27 phenotype, and there’s chronic inflammation particularly of the spinal joints, which particularly leads to sacral nerve root heath ectasia, although how that happens is really not clear.
So how do we investigate these patients? Well, MRI obviously is the cornerstone of identifying cysts. So here’s that patient with the multiple Tarlov cysts presenting with intracranial hypotension. MRI is excellent for demonstrating superficial siderosis in that NF1 case and for demonstrating the dural ectasia in the sacrum and lumbar spine. It can be relatively subtle though.
This is a 16-year-old girl with Marfan syndrome. Definitely dural ectasia but not as pronounced as the other cases that I’ve shown you. But she’s presented with intracranial hypotension. She’s known to have Marfan syndrome and she does have this dural ectasia. Obviously MR is best for showing the cranial signs of intracranial hypotension.
This is the same case, the young 16-year-old girl demonstrating there’s a nerve root cyst here which might give you the impression that that’s the origin of the leak. Myelography is essential but difficult. This is the NF1 patient. And the problem, of course, with big meningocele like this is that when you put the contrast in and you try to follow it, it just dives into this big pool and it can be very difficult to really outline the fine details. And we found it very difficult to work out this patient. This is the NF1 patient, multiple meningoceles in the thorax. How that caused the superficial siderosis is unclear but presumably related to that in some way, possibly a leak here although we think that was an artifact.
CT myelogram in these patients I think is particularly difficult. We saw those cases earlier where there’s leak in the sacrum. But in our experience is very difficult, because that’s very difficult to identify, because the dura just lines the bone and very difficult to see any space there where contrast can come out. It’s possible that there are leaks in that kind of space that cannot be identified.
This is the girl with Marfan syndrome where we thought perhaps it was that, but she’s actually got a small disc protrusion in the thoracic spine and that was where the leak was from, that disc protrusion. She had a type 1 leak and that’s the ventral dural defect from the type 1 leak. So particularly difficult in these patients to identify the site of leak because there are so many possible locations where they can leak from.
So how do we treat these patients? Well, I think it’s really, really difficult. Blood patch is the first line definitely, and we’ve actually had pretty good results, particularly with our Marfan patients, with blood patch. I’ve always found it interesting to know how the radiologists are confident they can get the needle into the epidural space for these patients because there doesn’t really seem to be much of an epidural space and the dura is so thin, but they seem to be able to do a good job and they respond, in our experience, very well to that. We try to avoid doing anything open.
Obviously, in a case where we can identify a ventral leak, approaching that surgically is a preferable treatment. And this is the patient with the superficial siderosis. What we decided to do here was, in an effort to prevent the progression of siderosis, was to resect those meningoceles. And I hope what you can appreciate here is how thin the dura is. Some of the tricky things here, of course, is that there is a nerve root that comes out through this cyst. And so we’re trying to preserve the nerve root.
And hopefully what you can see here is how thin that dura is peeling it off the pedicle. That was just very thin dura coming off the pedicle. This is a fascial graft that they are now suturing to the edges of the dura that we’ve defined, just in an effort to hopefully prevent whatever it is that from the meningocele that is allowing blood to come into the intradural space. Now whether that’s effective or not, that’s a bit of tissue from the outside, and postoperatively on postoperative MR we could not identify any longer any connection between the intradural space and the extradural space. There’s clearly still fluid in the meningocele – whether that’s CSF or not I don’t know. We haven’t repeated the myelogram, and whether he’ll progress with the siderosis or not is hard to know. So that’s the operation that we did, but clearly not simple and I think of uncertain benefit.
But then there’s dural reduction surgery, and that’s not something that we’ve done. We’re certainly trying to avoid doing that, but it has certainly been reported. Different techniques—plication, imbrication, resection of dura and closing the dura—are things that could be considered. But I think we would all recognize, particularly in the sacrum and lower lumbar spine, that would be fraught with postoperative complication difficulty. So we’ve avoided that. I know that others have done that, but results I think are unclear.
So in conclusion, I think this condition in association with dural ectasia is especially difficult. I say especially because our team finds SIH particularly difficult to treat overall. And it’s for the dural ectasia patients even more so very difficult to identify the site of leak. Having said that, blood patch does seem to work pretty well, particularly for the Marfan patients. And when we turn to surgery, I think the results are still unclear, but worth considering in patients who are otherwise desperate. Thanks for attention.