In this episode, Lyell K. Jones Jr, MD, FAAN, speaks with Jeremy K. Cutsforth-Gregory, MD, FAAN, who served as the guest editor of the June 2025 Disorders of CSF Dynamics issue. They provide a preview of the issue, which publishes on June 2, 2025.

Dr. Jones is the editor-in-chief of Continuum: Lifelong Learning in Neurology® and is a professor of neurology at Mayo Clinic in Rochester, Minnesota.

Dr. Cutsforth-Gregory is an associate professor in the department of neurology at Mayo Clinic in Rochester, Minnesota.

Additional Resources

Read the issue: continuumjournal.com

Subscribe to Continuum®: shop.lww.com/Continuum

Continuum® Aloud (verbatim audio-book style recordings of articles available only to Continuum® subscribers): continpub.com/Aloud

More about the American Academy of Neurology: aan.com

Social Media

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@ContinuumAAN

Host: @LyellJ

Guest: @JCGneuro

Full episode transcript available here

Interview with Jeremy Cutsforth-Gregory, MD

Dr Jones: Most of the time when neurologists think about cerebrospinal fluid or CSF, we're thinking about getting a sample so we can test it for biomarkers of infection or inflammation, tumors, more recently neurodegenerative diseases. But there are many patients for whom the CSF isn't a clue to the problem---it is the problem. Today I have the opportunity to interview Dr Jeremy Cutsforth-Gregory, who is the guest editor of our first-ever issue at Continuum on disorders of CSF dynamics.

Dr Jones: This is Dr Lyell Jones, Editor-in-Chief of Continuum. Thank you for listening to Continuum Audio. Be sure to visit the links in the episode notes for information about subscribing to the journal, listening to verbatim recordings of the articles, and exclusive access to interviews not featured on the podcast.

Dr Jones: This is Dr Lyell Jones, Editor-in-Chief of Continuum: Lifelong Learning in Neurology. Today I'm interviewing Dr Jeremy Cutsforth-Gregory, who recently served as Continuum's guest editor for our latest issue, which covers disorders of CSF dynamics. Dr Cutsforth-Gregory is an associate professor in the Department of Neurology at Mayo Clinic in Rochester, Minnesota, where he's also the director of the Mayo Clinic CSF Dynamics Clinic and an assistant dean of career advising at the Mayo Clinic School of Medicine. Dr Cutsforth-Gregory, welcome, and thank you for joining us today. Why don't you introduce yourself to our listeners?

Dr Cutsforth-Gregory: Thank you so much, Dr Jones. I'm excited to be here and really privileged to have served as the guest editor for this first issue devoted to CSF dynamics. You mentioned my title as director of the CSF Dynamics Clinic, in which we brought together what we think of as the full spectrum of disorders where pressure or flow of the fluid around the central nervous system is off. So, we do CSF leaks, we do intracranial hypertension and normal pressure hydrocephalus, and from that have been able to gain quite a few insights that I'm excited to share with you today.

Dr Jones: Yeah. And I'm really grateful for your time. I'm really grateful for this issue. You know, we all learn about disorders of CSF flow in training, but my impression---and maybe you share it, Dr Cutsforth-Gregory---is that many of these patients fall through the cracks. I think there's probably many reasons for this. I think it's in part because some aspects of this practice are relatively new or they're changing rapidly, or some of the disorders are uncommon. And I think many of these require a high degree of coordination between neurologists and neurosurgeons and radiologists. So we thought a Continuum issue dedicated to this would help close some practice gaps that we're pretty confident are out there. I'm really grateful for your leadership of it, and I think it'll come in handy for junior readers and even our more experienced listeners as well. And let's get right to it. You've had a chance now to review all of the articles in the issue and, you know, the latest in the field. What's the biggest thing that you would like to see change in the care of these patients?

Dr Cutsforth-Gregory: I think you're right that there is often delay in diagnosis, incorrect diagnosis, misdiagnosis, really across the spectrum of the low pressure, high pressure and normal pressure disorders. And that's what I'd like to see change with this issue, is increased awareness of the really myriad presentations that spontaneous intracranial hypotension can have. It's not all orthostatic headache, although that's common. Similarly, idiopathic intracranial hypertension is misdiagnosed in a third or more cases presenting to ophthalmology clinics. So, it's not just papilledema, high pressure in a certain demographic. And I think the article by Dr Aileen Antonio really goes into the details on how to make an accurate diagnosis and not miss these and not mistreat them. And normal pressure hydrocephalus, the pendulum has really swung between whether this is an entity or isn't an entity. It is. It's patients we can help. The imaging findings are surprisingly common, and the disorder is probably somehow both overcalled on CT scans of the head---cannot rule out normal pressure hydrocephalus, clinical correlation required, we've all seen that report---but also missed opportunities to help patients who have treatable gait, cognitive and bladder disorders. So, if we could improve awareness and increase the accuracy of diagnosis on these three disorders, I will say the mission has really been moved forward.

Dr Jones: Thanks for that. Let's start with NPH because again, over my career, I have seen the pendulum swing back and forth in terms of awareness of this disorder and thresholds for diagnosis. What's our latest in terms of the understanding of normal pressure hydrocephalus and how should our listeners think about the approach to diagnosing these patients?

Dr Cutsforth-Gregory: I think we all learn that NPH is dementia, gait disorder and urinary incontinence, and that hasn't changed. A good chunk of these patients, perhaps half or more, don't have the full triad, and you do not have to have the full triad for the diagnosis or to justify intervention with permanent CSF diversion through shunt placement. And so, being open to the diagnosis in a patient with a gate apraxia, which is usually the first leading present presenting change which is a gait disorder. Cognitive changes follow that, bladder comes along the way. So, I think anytime you see someone with an unexplained gait disorder that has apraxic features, short steps, three steps to turn, can look a little Parkinsonian but you don't have other Parkinsonism on exam necessarily, we should be thinking about NPH and ordering a good-quality head imaging to look for those features.

Dr Jones: Yeah, thanks for that point, Jeremy. It does seem like the pendulum has swung back and forth on the diagnosis of this disorder. And I think in many ways it comes down to having good diagnostic biomarkers. A term that I know… I was only made aware of it a few years ago: disproportionately enlarged subarachnoid space hydrocephalus, or DESH. So, tell us a little bit more about that. It's not just about the ventricles, right?

Dr Cutsforth-Gregory: That's exactly right. So, we think hydrocephalus, that means ventriculomegaly, and it does, but DESH, as you said, the mouthful “disproportionately enlarged subarachnoid space hydrocephalus”, is basically CSF accumulation around the brain outside the ventricles. Common features would be enlarged Sylvian fissures, focally dilated sulci, and then at the same time, up high on the convexity, tight sulci. So, it's this combination; there's clearly a flow problem where CSF is being trapped in certain areas outside the brain and excluded from others. And that is a common feature. And that alone predicts a positive response to shunt surgery.

Dr Jones: I remember the first time one of my colleagues pointed that out to me on an image, and it just made me wonder how many times I had missed it before that point in my career. But that's the point, is to learn and move forward. One of the common themes, I think, in this practice, one of the common themes in this issue, is the interdisciplinary work that's necessary not just for treating patients with CSF dynamics disorders, but also the diagnosis. We really do have to work carefully and closely with neurosurgeons and with radiologists. And to reflect that we had a pretty diverse group of authors. Moreso, I think, that we usually do for Continuum, given the overlap with the radiology and surgical practice. As you were reviewing these articles, were there any unique or distinctive perspectives that you saw come through?

Dr Cutsforth-Gregory: Absolutely. And I have to say, I'm so proud of the diverse author panel we were able to put together: as you said, including clinicians, but also neuroradiologists; neurosurgeons, both adult and pediatric; as well as a couple- an ENT surgeon to talk about those cranial skull base leaks. So, we really brought together what we think is necessary to take care of these patients. As far as unique perspectives here, I would point to the article on diagnosis, surgical treatment, the long term implications of atraumatic cranial CSF leaks. So, these are the patients who present with CSF otorrhea or rhinorrhea and do not have a history of skull base surgery or trauma to explain it. That is often a chronic intracranial hypertension patient who, instead of staying sealed up and building up pressure and presenting with papilledema and headaches, had a leak. And that's relevant because, after it’s fixed, that patient needs to come to us in neurology to be monitoring for papilledema, measure lumbar puncture, open pressure. And we've developed that as part of our workflow with our colleagues in neurosurgery and ENT who seal those leaks, because that's a patient who is at high risk of recurrent leak if we don't treat the underlying high pressure disorder. That's a new concept, I think, for many of us. And so, to be able to put that front and center in an article, in an issue for practicing neurologists, I think, is really important, and it's something we haven't been able to do before.

Similarly, the article by Dr Olga Fermo on the treatment of persistent symptoms after normalization of CSF pressure. We've all taken care of patients who had a CSF leak or had hypertension, and it seems like those issues are resolved, and yet they still have headaches. The IIH treatment trial taught us that that happens in perhaps two thirds of patients with IIH. And so, to have Dr Fermo's article on how to help those patients manage the headaches when the CSF disorder seems to have been resolved, I think it's super useful. The last one I would mention is just the final one by Dr Shenandoah Robinson, a pediatric neurosurgeon, talking about child onset hydrocephalus. And so, NPH is the focus of most of those other articles. But the patients who we will take care of as adult neurologists, child neurologists, whose issue really started early on, it’s important that we stay involved and how to do that, what things we should be watching for, when to suspect shunt malfunction, it’s all covered in Dr Robinson's article, and it’s a unique one for this issue.

Dr Jones: It's always interesting to read articles, as a neurologist, that are written by a neurosurgeon because, you know, they have a different perspective, right? T're intervening on the anatomy, and just hearing how they think about these things was illuminating for me. The article on atraumatic cranial skull base CSF leaks, that connection with intracranial hypertension, I was unaware of that. So that was a good learning point for me. And while we're still on the too-high-pressure problem of idiopathic intracranial hypertension, do we have any more insight into what causes that? What's the mechanism of that disease? Do we know any more than we used to?

Dr Cutsforth-Gregory: We know more than we used to. We certainly don't understand all of it. But rather than just a disease of reproductive-age women carrying extra weight, it is now recognized as, really, a metabolic and hormonal-driven condition. And it's relevant because it really highlights new ways to intervene and to treat these patients. The GLP-1 inhibitors may have a role, considering some of the comorbidities like polycystic ovary syndrome and the hormonal connections. The patients who perhaps are female-to-male trans, who then can present with intranial hypertension, and how we can help them without needing to take them off gender confirming hormone therapy, is all really relevant to help us help more patients by having that broader understanding of the cause of disease, that it’s not just weight gain/weight loss.

Dr Jones: Fantastic, and very useful to know. Thinking of the other end of the spectrum, right, rather than too much CSF or too much CSF pressure… I know this has been a focus of your academic work, Dr Cutsforth-Gregory. We also have disorders of CSF hypotension where the pressure is too low, and that this is usually reflective of a dural defect. I know in my own practice, sometimes, these are very difficult to find, and that's really- as you said, diagnosis is the first step, but then we have to find the problem and try to direct surgeons where to go to repair it. Do you have any tips for our listeners on how to approach the hunt for the source of CSF leaks?

Dr Cutsforth-Gregory: Absolutely. And I first have to give a call out to my mentor, Dr Bahram Mokri, who is the one who first reported the diffuse sterile enhancement, back in the early 1990s, that marks some, but not all, patients with spontaneous intracranial hypotension. He would also remind me that that's not a good term to call it, even though I just did and I will continue to do it intermittently. Because really, this is an underlying spinal CSF leak or a CSF venous fistula. And the problem is not too-low pressure, which is why hypotension is probably not the best word, but too-low volume. It's intracranial CSF hypovolemia. You know, with the opportunity that Dr Mokri gave me to see some of those patients with him and become intrigued by it, it is the bulk of my clinical practice, my research focus, and the conversations I get to have every single day with neuroradiologists and neurosurgeons. I tell patients, it is a field that is moving incredibly quickly and that, when I see them again in a few months or the next year, for whatever reason, I always joke and I say, I reserve the right to have different recommendations, because it is moving. I finished residency in 2014, which is the year CSF fistulas were first reported. I'm sure they existed before that. So, it was a lack of awareness. And so, look for what you know. Now we know to look for fistulas. You find what you look for; we've developed a number of new myographic techniques to find these things, and they are now the majority of the type of leak that we find. So, it is a patient population where we were missing more than we were hitting ten years ago. And now maybe that's still true, but we're certainly finding a lot more than we used to because of those collaborations.

Dr Jones: Thinking back to DESH, right? Once you're aware that it is something that can be identified, you start to see it more and more. And again, that's how we move the field forward. And again, the CSF venous fistula story is one that I know was relatively new to me and something I learned a lot about reading through the issue. And hopefully our readers and our listeners find some insights and benefits there. This is a rapidly changing field. This may be a hard question to answer, but when you look into the future, what are some of the changes on the horizon in this practice?

Dr Cutsforth-Gregory: See, I'll probably point to the- both diagnosis and treatment. We're recognizing that it's, like I said earlier, not all orthostatic headache, but some of the other manifestations, such as frontotemporal brain sagging syndrome, can be a manifestation of leak. So, suspected leak is the first step. Then you have to look for it. And MRI will change, you know, incrementally, I'm sure; we'll get higher resolution pictures. But the C wave of change is going to be in how to do the myelogram, what imaging modality we use; and the newest kit on the block, if you will, is photon-counting detector CT myelography. That's a different kind of CT scanner than we've been used to over the last few decades. It detects light energy differently. It allows better signal-to-noise ratio, faster acquisition of scans. And so, using that allows us to get thinner slices through the spine to look for leaks and fistulas. I think photon CT will become more widespread because it has applications well beyond neurology and just myelograms.

And so, as those scanners become more available, everyone will get to be better at finding these leaks. And then treatment, I'll highlight a procedure called transvenous paraspinal vein embolization. You know, a CSF venous fistula is an abnormal connection between a nerve root sleeve and a vein. And the CSF is escaping up through the that vein in an unregulated fashion. And historically when those were found, the treatment was to ligate the nerve root. Get rid of the nerve root sleeve, you get rid of the abnormal connection, you get rid of the vein, you stop the leak. And that is effective. A number of studies have shown that. But it's also invasive; it requires a laminectomy and losing a nerve root. You can't do that at every level of the spine, right? This is predominantly thoracic, and only if you're away from the artery of Adamkiewicz. But a few years ago, Dr Walid Benjigchi pioneered a procedure of going through the vein and embolizing it, putting in a liquid embolic agent that seals it off. The nerve root stays attacked. We can do it at every level of the spine, and it's an outpatient, endovascular procedure to fix fistulas. That kind of minimally invasive procedure for fistulas has been a major shift away from the open surgeries. We will, I think, make advances with new catheters and new needles to be able to do some other kind of minimally invasive procedures for the other kinds of leaks. I think that's what we'll be seeing, is less and less invasive procedures on the leak side.

Dr Jones: Great summary there. Thank you. So, it sounds like a combination of hopefully improved clinician awareness, which will improve diagnostic recognition; more sensitive tools like the photon counting CTS; and less invasive definitive therapies, which I think is promising for the field. And you've led a lot of that work, Dr Cutsforth-Gregory, over the last few years. When you see these patients, I'm sure it's rewarding to see patients with previously poorly-recognized or misunderstood symptoms get better. Is that the most rewarding part of this practice for you, or what can you tell me about your experience in the care of these patients?

Dr Cutsforth-Gregory: You know, I'm a curious person. I like to learn. So, I will say it is really rewarding to develop a new technique and put it into practice and see it increase our hit rate on finding these leaks and helping these patients. But nothing beats the feeling of taking a patient who's been stuck in bed or saying that they can't function and they're out of work or out of their family life, and getting that Christmas card or that hug that says they're back. But, you know, we're here to help our patients, and nothing can beat that feeling.

Dr Jones: I think that's a great point to end on. Dr Cutsforth-Gregory, thank you for joining us. Thank you for such a detailed discussion of a broad, diverse topic. I learned a lot today---some things that I wasn't aware of, having read the issue---and hopefully our listeners did, too.

Dr Cutsforth-Gregory: Thank you so much, Dr Jones.

Dr Jones: Again, we've been speaking with Dr Jeremy Cutsforth-Gregory, Guest Editor of Continuum's first-ever issue focusing on CSF dynamics. Please check it out. And thank you to our listeners for joining today.

Dr Monteith: This is Dr Teshamae Monteith, Associate Editor of Continuum Audio. If you've enjoyed this episode, you'll love the journal, which is full of in-depth and clinically relevant information important for neurology practitioners. Use the link in the episode notes to learn more and subscribe. Thank you for listening to Continuum Audio.