Progressive supranuclear palsy and corticobasal syndrome are closely related neurodegenerative disorders that present with progressive parkinsonism and multiple other features that overlap clinically and neuropathologically. Early recognition is critical to provide appropriate treatment and supportive care.

In this episode, Teshamae Monteith, MD, FAAN speaks with Nikolaus R. McFarland, MD, PhD, FAAN, author of the article "Progressive Supranuclear Palsy and Corticobasal Syndrome" in the Continuum® August 2025 Movement Disorders issue.

Dr. Monteith is the associate editor of Continuum® Audio and an associate professor of clinical neurology at the University of Miami Miller School of Medicine in Miami, Florida.

Dr. McFarland is an associate professor of neurology at the University of Florida College of Medicine at the Norman Fixel Institute for Neurological Diseases in Gainesville, Florida.

Additional Resources

Read the article: Progressive Supranuclear Palsy and Corticobasal Syndrome

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Full episode transcript available here

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 earning CME, subscribing to the journal, and exclusive access to interviews not featured on the podcast.

Dr Monteith: Hi, this is Dr Teshamae Monteith. Today I'm interviewing Dr Nikolaus McFarland about his article on progressive supranuclear palsy and cortical basilar syndrome, which appears in the August 2025 Continuum issue on movement disorders. Welcome, how are you?

Dr Farland: I'm great. Thank you for inviting me to do this. This is a great opportunity. I had fun putting this article together, and it's part of my passion.

Dr Monteith: Yes, I know that. You sit on the board with me in the Florida Society of Neurology and I've seen your lectures. You're very passionate about this. And so why don't you first start off with introducing yourself, and then tell us just a little bit about what got you interested in this field.

Dr Farland: I'm Dr Nicholas McFarlane. I'm an associate professor at the University of Florida, and I work at the Norman Fixel Institute for Neurological Diseases. I am a director of a number of different centers. So, I actually direct the cure PSP Center of Care and the MSA Center of Excellence at the University of Florida; I also direct the Huntington's clinic there as well. But for many years my focus has been on atypical parkinsonisms. And, you know, I've treated these patients for years, and one of my focuses is actually these patients who suffer from progressive supranuclear palsy and corticobasal syndrome. So that's kind of what this review is all about.

Dr Monteith: You probably were born excited, but I want to know what got you interested in this in particular?

Dr Farland: So, what got me interested in this in particular was really the disease and the challenges that's involved in it. So, Parkinson's disease is pretty common, and we see a lot of that in our clinic. Yet many times, roughly about 10 to 15% of my patients present with these atypical disorders. And they're quite fascinating. They present in different ways. They're fairly uncommon. They're complex disorders that progress fairly rapidly, and they have multiple different features. They're sort of exciting to see clinically as a neurologist. I think they're really interesting from an academic standpoint, but also in the standpoint of really trying to bring together sort of a team. We have built a multidisciplinary team here at the University of Florida to take care of these patients. They require a number of folks on that team to take care of them. And so, what's exciting, really, is the challenge of treating these patients. There are very limited numbers of therapies that are available, and the current therapies that we have often really aren't great and over time they fail. And so, part of the challenge is actually doing research. And so, there's actually a lot of new research that's been going on in this field. Recently, there's been some revisions to the clinical criteria to help diagnose these disorders. So, that's really what's exciting. The field is really moving forward fairly rapidly with a number of new diagnostics, therapeutics coming out. And hopefully we can make a real difference for these patients. And so that's what really got me into this field, the challenge of trying to treat these patients, help them, advocate for them and make them better.

Dr Monteith: And so, tell me what the essential points of this article.

Dr Farland: So, the essential points, really, of this article is: number one, you know, just to recognize the new clinical criteria for both PSP and corticobasal syndrome, the diagnosis for these disorders or the phenotypic spectrum has really expanded over the years. So, we now recognize many different phenotypes of these disorders, and the diagnosis has gotten fairly complicated. And so, one of the goals of this article was to review those new diagnostic criteria and the different phenotypic ways these diseases present. I wanted to discuss, also, some of the neuropathology and clinicopathological overlap that's occurred in these diseases as well as some of the new diagnostic tests that are available. That's definitely growing. Some of the new studies that are out, in terms of research and clinical trials. And then wanted to review some of the approaches for treatment for neurologists. Particularly, we're hoping that, you know, this article educates folks. If you're a general neurologist, we're hoping that recognizing these diseases early on will prompt you to refer these patients to specialty clinics or movement disorder specialists early on so they can get appropriate care, confirm your diagnosis, as well as get them involved in trials if they are available.

Dr Monteith: And how has the clinical criteria for PSP and cortical basilar syndrome changed?

Dr Farland: I think I already mentioned there's been an evolution of the clinical criteria for PSP. There's new diagnostic criteria that were recently published, and it recognizes the multiple clinical phenotypes and the spectrum of the disease that's out there, which is much broader than we thought about. Corticobasal clinical criteria are the Dr Armstrong criteria from 2013. They have not been updated, but they are in the works of being updated. But it does recognize the classic presentation of corticobasal syndrome, plus a frontal executive predominant and then a variant that actually overlaps with PSP. So, there's a lot more overlap in these two diseases than we originally recognized.

Dr Monteith: And so, you spoke a bit about FTD spectrum. So why don't you tell us a little bit about what that is? I know you mentioned multiple phenotypes.

Dr Farland: What I really want to say is that both PSP and corticobasal syndrome, they're relatively rare, and what- sort of as to common features, they both are progressive Parkinson disorders, but they have variable features. While they're commonly associated with Parkinson's, they also fit within this frontotemporal lobar spectrum, having features that overlap both clinically and neuropathologically. I just want folks to understand that overlap. One of this pathological overlap here is the predominant Tau pathology in the brain, an increasing recognology- recognition of sort of the pathological heterogeneity within these disorders. So, there's an initial description, a classic of PSP, as Richardson syndrome. But now we recognize there are lots of different features to it and there are different ways it presents, and there's definitely a lot of clinical pathological overlap.

Dr Monteith: Why don't we just talk about some red flags for PSP?

Dr Farland: Yeah, sure. So, some of the red flags for PSP and even corticobasal syndrome are: number one is rapid progression with early onset of falls, gait difficulty, falling typically backwards, early speech and swallow problems that are more prominent than you see in Parkinson's disease, as well as eye gaze issues. So, ocular motor features, particularly vertical gaze palsy. In particular what we talk about is the supranuclear gaze palsy, and one of the most sensitive features that we've seen with these is downgaze limitation or slowed downgaze, and eventually a full vertical gaze palsy and followed supranuclear gaze palsy. So, there's some of the red flags that we see. So, while we think about the lack of response to levodopa frequently as something that's a red flag for Parkinson's, there are many times that we see Parkinson's patients, and about a quarter of them don't really respond. There's some features that don't respond to levodopa that may not be so specific, but also can be helpful in this disease.

Dr Monteith: And what about the red flags for cortical basilar syndrome?

Dr Farland: So, for cortical basilar syndrome, some of the red flags again are this rapidly depressive syndrome tends to be, at least in its classical present presentation, more asymmetric in its presentation of parkinsonism, with features including things like dystonic features, okay? For limb dystonia and apraxias---so, inability to do a learned behavior. One of those red flags is a patient who comes in and says, my hand doesn't work anymore, which is something extremely uncommon that you hear in Parkinson's disease. Most of those patients will present, say, I might have a tremor, but they very rarely will tell you that I can't use my hand. So look out for that sign.

Dr Monteith: And let's talk a little bit about some of the advances in the fields you mentioned, evolving biomarker and imaging capacities. So, how are these advances useful in helping us understand these conditions, especially when there's so much heterogeneity?

Dr Farland: I might start by talking a little bit about some of the clinical criteria that have advanced. Why don't we start there and just discuss some of the advances? I think in PSP, I think, originally we had both probable and possible diagnoses of PSP, and the diagnostic criteria were basically focused on what was what's called "classical PSP" or "Richardson syndrome". But now we recognize that there are multiple phenotypes. There's an overlap with Parkinsonism that's slower in progression and morphs into PSP, the classical form. There's a frontal behavioral variant where patients present with that frontal behavioral kind of thing. There's a speech-language variant that can overlap with PSP. So they have prominent speech language, potentially even apraxia speech. So, recognition of these different phenotypes is sort of a new thing in this field. There's even overlap with cortical basal syndrome and PSP, and we note that the pathology can overlap as well. So, I think that's one of the things that have changed over time. And these were- recently came out in 2017 in a new publication in the Movement Disorders Society. So, in terms of diagnostic tests as well---and there's been quite a bit of evolution---really still to date, our best diagnostic test is imaging. MRI is really one of our best tests currently. Currently blood tests, spinal fluid, there's new biomarkers in terms of skin… they're still in the research phase and not necessarily very specific yet. So, we rely heavily on imaging still; and for PSP, what we're looking for largely are changes in the brain stem, and particularly focused on the midbrain. So disproportionate midbrain atrophy compared to the pons and the rest of the midbrain is a fairly specific intensive sign for PSP. Whereas in MSA we see more of a pontine atrophy compared to the midbrain. So that can be really helpful, and there are lots of different new measurements that can be done.

PET scans are also being used as well. And there are new PET markers, but they still remain kind of research-based, but are becoming more and more prevalent and may be available soon for potential use. Although there's some overlap with PET tracers with Alzheimer's disease and different Tau isoforms. So, something to be wary about, but we will be seeing some of these soon coming out as well. More kind of up-to-date things include things like the spinal fluid as well as even some of the skin biopsies. And I think we've heard some word of recent studies that have come out that potentially in the very near future we might actually have some Tau protein tests that we can look at Tau either in spinal fluid or even in a skin biopsy. But again, still remains research-based and, we still need more information as to whether these tests can be reproducible and how sensitive or specific they are.

Dr Monteith: It sounds like, when really approaching these patients, still, it's a lot of back to the history, back to the clinical and some basic imaging that we should be able to identify to distinguish these types of patients, and we're not quite where we need to be yet for biomarker.

Dr Farland: I totally agree with you. I think it starts, really, with the clinical exam and that's our main focus here; and understanding some of the new clinical criteria which are more sensitive, but also specific, too. And they're really useful to look at. So, I think reviewing those; patients do progress, following them over time can be really useful. And then for diagnosis, getting imaging if you suspect a patient has an atypical presentation of parkinsonism, to look for signs or features that might be specific for these different disorders.

Dr Monteith: Why don't we take a typical case, a typical patient that you would see in clinic, and walk us through the thought process---especially, maybe they presented somewhat early---and the different treatment approaches to helping the patient, and of course their family.

Dr Farland: Yeah, sure. So, a typical patient might be someone who comes in with, like, a three year history of progressive gait problems and falling. And let's say the patient says, I'm falling backwards frequently. They may have had, like, a rib fracture, or they hit their head once, and they're describing some speech issues as well. Now they're relying on a walker and family members saying they rarely let them be by themselves. And there may be some slowing of their cognitive function and maybe a bit of withdrawal. So that's a typical patient. So, the approach here is really, what are some of the red flags? I think already you hear a red flag of a rapidly progressive disease. So, Parkinson's disease patients rarely have frequent falls within the first five years. So, this is within three years or less. You're already hearing early onset of gait problems and falling, and particularly falling backwards rather than forwards as often Parkinson's disease patients do. You're hearing early speech problems and maybe a subtle hint of cognitive slowing and some withdrawal. So, a lot of things that sort of are red flags. So, our approach really would be examining this patient really closely. Okay? We'd be listening to the history, looking at the patient. One thing is that some of these patients come in, they may be in a wheelchair already. That's a red flag for us. If they're wearing sunglasses---sometimes we see that patients, they have photosensitivity and they're in a chair and they're wearing sunglasses---you take the glasses off and you look at their face and they have that sort of a facial stare to them---not just the masked face, but the stare---and their eyes really aren't moving. So, another kind of clue, maybe this is probably something atypical, particularly PSP is what I'm thinking about.

So, the approach is really, do a thorough exam. I always recommend looking at eye movements and starting with volitional saccades, not giving them a target necessarily, but asking them to look up and then look down. And then particularly look at the speed of downgaze and whether they actually have full versions down, are able to do that. That's probably your most sensitive test for a patient who has PSP. Not the upgaze, which can be- upgaze impairment in older patients can be nonspecific. So, look for that down gaze. So, if I can get out one message, that's one thing that can be easily done and examined fairly quickly for diagnosis of these patients. And then just look for signs of rigidity, bradykinesia, maybe even some myelopraxia, and then look at their gait carefully so that there's a high suspicion. Again, if there's some atypical features, imaging is really important. So, my next step would be probably getting an MRI to evaluate whether- do they have brain somatrophy or other widespread atrophy or other signs? You need to think about your differential diagnosis for some of these patients as well. So, common things are common; vascular disease, you can't have vascular parkinsonism or even signs of NPH. Both of those can present with progressive gait difficulty and falls. So, the gait may look more like Parkinson's rather than ataxic gait that we see in classic PSP, but still they have early gait issues, and that can be a mimicker of PSP, So looking for both of those things in your imaging. Think about sort of autoimmune potentially causes. So, if they have a really rapid progressive cause, there are some rare autoimmune things. There have been recent reports of things like IgLON5, although there's limited cases, but we're doing more screening for some of those autoimmune causes. And then even some infectious causes like Whipples, that are rarely present like this. Okay? And have other signs and features.

Dr Monteith: So, let's say you diagnose this patient with PSP and you're assessing the patients to see how you can improve their quality of life. So, what are some potential symptomatic managements that will help our patient?

Dr Farland: I recommend for most all of these patients… while the literature indicates that many patients with PSP, and especially corticobasal syndrome, don't respond well to levodopa. So, the classic treatment for parkinsonism. However, we all recommend a trial of levodopa. These patients may respond partially to doses of levodopa, and we try to push the doses a bit higher. So, the recommended trial is usually a dose up to roughly 1000 milligrams of levodopa per day. And give it some time, at least two, if not actually three months of a trial. If not well-tolerated, you can back off. If there's no response at all or no improvement, then slowly back off and taper patients off and ask them to tell you whether they feel like they're actually worsening. So, many patients, sometimes, don't recognize the improvements, or family members don't recognize it until we actually taper them back off. And they may end up saying there are some other things that even recognize. Even some nonmotor benefits can be seen with levodopa. In some cases, we do keep them on levodopa, but levodopa's our best therapy for this. Dopamine agonists, MAO inhibitors, have all been sort of tried and they've been studied, but often don't really help or fail to help benefit these patients and could be fraught with some other side effects.

I think many people do also turn to Amantadine as a treatment for Parkinson's, gait problems, freezing, if you see it in these disorders. Yet Amantadine is fraught with issues of side effects, including cognitive issues, and I think is not well-tolerated. But there are the rare patient who actually does respond to this or claims they respond to this. By and large, these patients relentlessly progress, unfortunately. So, beside treatment of other symptoms, I think it's really important to recognize that they require supportive cares and therapy. So, starting those early on and getting your allied healthcares kind of involved. So that includes people like physical, occupational therapy for the gait issues, the falls, occupational therapy for doing daily activities. Speech language pathology can be really a critical player for these because of the early speech and language issues, as well as swallow difficulties. Swallow is compared quickly in these patients. And so, we do recommend the screening evaluation, then often following patients either every six- or even annually, at least, with a swallow evaluation. And we recommend the fluoroscopic-guided kind of modified barium swallow for these patients.

Dr Monteith: And how does that differ if, let's say, the patient had cortical basilar syndrome? What are some of the symptomatic treatments that would be high on your consideration?

Dr Farland: So actually, these patients also have a very similar approach, and they often have some overlapping features. Maybe a little bit of difference in terms of the level of apraxia and some dystonic features that you see in corticobasal syndrome. So, as I mentioned earlier that these patients have a more typ- when they present, typically have a more asymmetric presentation. And one of the biggest issues is this limb apraxia. They may have abnormal movements as well as, like, the alien limb-type phenomena as well. So, the focus of therapy, while similar in the sense we focus on the parkinsonism, I do always try levodopa and try to ramp up the doses to see if it benefits. It does often fail, but it's definitely worth trying. The other focus of these patients is trying to treat symptoms. Dystonia, those features… in some cases, we can help; if it's painful or uncomfortable, muscle relaxants can be used. If it's vocal, things like Botox can be really helpful. Often times it is more palliative than actually restorative in terms of function, but still can be really helpful for patients who ask about pain and discomfort and trying to treat. And then of course, again, the focus on our supportive care. We need to build that network and build that team of folks, the therapists, the physical, occupational, and the speech therapist to help them. If they have language problems---like either in PSP or corticobasal---I'll also include my request to a speech language pathologist to work on cognitive function. That's a special, additional thing you have to ask for and then specifically request when you make a referral to a speech language pathologist.

Dr Monteith: That is so important. I think keeping the simulation, keeping the social support, and I would probably guess that you would also include screening for sleep and mood disorder.

Dr Farland: Absolutely. Mood disorders are really big in these diseases. Patients are suffering terribly. You do hear about labile mood in both of these diseases, particularly PSP; and even what's called pseudobulbar palsy, where the mood is not always congruent with the affect. So they may laugh or cry inappropriately, and particularly the crying can be very disturbing to family and caregivers to see that. And so, treating those things can be really important. So always asking about the mood issues. Depression in particular is something that we're very sensitive about, and there is a higher incidence of suicidal ideations. Asking about that and feeling and making sure that they are in a safe environment can be really important.

Dr Monteith: Thank you so much.

Dr Farland: Thank you.

Dr Monteith: Today I've been interviewing Dr Nikolaus McFarland about his article on progressive supranuclear palsy and cortical basilar syndrome, which appears in the August 2025 Continuum issue on movement disorders. Be sure to check out Continuum Audio episodes from this and other issues, 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. AAN members, you can get CME for listening to this interview by completing the evaluation at continpub.com/audioCME. Thank you for listening to Continuum Audio.

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