A reader just commented, “What other diseases can mimic PSP?” Below is a pretty exhaustive list of things that can cause vertical gaze palsy*, the most specific** diagnostic hallmark of PSP. Most of these disorders don’t mimic the whole classic PSP syndrome, but even PSP doesn’t do that in many cases. Keep in mind that most of these mimics have other features besides the gaze palsy, occur at much younger ages than PSP, or are exceedingly rare. For all those reasons, a good neurologist is unlikely to confuse these conditions with PSP in practice.
The disorders with specific treatment (though maybe not cures) have three asterisks ***.
*”Palsy” in general means weakness (not tremor, as popularly thought). In the setting of PSP, palsy refers to a limitation of the range of voluntary eye movements.
**The “specificity” of a diagnostic sign is technically the fraction of the people without the disease who don’t have the sign. In other words, specificity = [true negatives] divided by [true negatives + false positives].
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DISORDERS WITH VERTICAL GAZE PALSY IN AT LEAST SOME CASES
Degenerative
- Amyotrophic lateral sclerosis
- Corticobasal degeneration
- Dementia with Lewy bodies
- Frontotemporal dementia with tau staining
- Frontotemporal dementia with ubiquitin staining
- Globular glial tauopathy
- Lytico-bodig
- Motor neuron disease with congophilic angiopathy
- Multiple-system atrophy
- Pallidal degeneration
- Parkinson disease (only upgaze affected)***
- PSP
Structural
- Normal-pressure hydrocephalus***
- Pineal region masses***
- Third ventricular enlargement***
Metabolic / Genetic
- B-12 deficiency***
- Huntington disease
- Neuronal intranuclear inclusion disease
- Niemann-Pick disease type C***
- Spinocerebellar ataxia type 8
- Tay-Sachs disease, adult-onset (hypometric vertical saccades)
- Wernicke encephalopathy***
- Wilson disease***
Immune
- Anti-phospholipid syndrome***
- Anti-IgLON4 disease***
- Paraneoplastic syndromes***
- Postencephalitic parkinsonism***
Vascular
- Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL)
- Lacunar states (“vascular PSP”)***
- Post-aortic surgery
Infectious
- Whipple disease***
- Neurosyphilis***
Toxic
- Guadeloupean tauopathy
Prion
- Creutzfeldt-Jakob disease
PSP Blog 
Hi Dr G, which type of specialist is best able/willing to do this type of workup? Some of these diseases seem to span various specialties, including genetics, rare disease, infectious diseases, etc. Even PSP neurologists as top tier academic institutions have declined to do involved ‘mimicking’ workups, and PCPs say it falls outside their scope and to find a specialty physician. Additionally, do you know of any documentation that shares the specific tests that should be ordered? It seems like some of these disorders may involve a simple blood test as a first step, but even if that test is negative, could require more invasive testing to definitively rule out a ‘mimicking’ disorder. This ‘mimicking’ issue is definitely a challenge for patients who may only have ‘suspected’ or ‘possible’ PSP, but can’t find a PSP center willing to work them up for these other disorders. Thanks for any information or more help in shedding light on this issue for families.
Dear C:
Keep in mind that most of the “PSP mimics” in my last post don’t mimic PSP in very many features. The list was just disorders with abnormal vertical gaze, which is only one feature of PSP. As a practical matter, 99 of every 100 people with the classic features of PSP occurring at a typical age, in a typical order, and with a typical rate of progression have PSP. But there are atypical cases.
I assume by “PSP neurologists” you’re referring to neurologists specializing in movement disorders or behavioral neurology. In my experience, such neurologists are quite comfortable ordering the tests to rule out almost all of the PSP mimics that might not be evident from a good history and neurological exam and routine brain MRI. These include genetic tests and other blood tests. True, they may not be familiar with the testing appropriate for Niemann-Pick disease type C and some of the immune-mediated conditions, but they should be. Those diseases either occur at younger ages (NPC3) or progress faster (immune conditions) than real PSP. But I’ll work on a post providing some systematic guidance in ferreting out PSP mimics – what we call “differential diagnosis” – for some time in the near future. Meanwhile, your neurologist is welcome to contact me through CurePSP (golbe@curepsp.org) for informal advice.
C: As soon as I have the time, I’ll post a list of how physicians can start working up and possibly treating the PSP mimics where that’s possible. Dr. G
Thank you very much Dr G! I think this information could greatly help folks who may have another disorder that mimics PSP (or that mimics other Atypical Parkinsonian disorders like DLB/LBD and others).
For some of these ‘mimicking disorders’ workups, it looks like they can include both non-invasive blood tests, as well as more invasive tests (CSF tests, skin tests, procedures etc). In these cases, if it’s possible to include which tests should be used to truly/definitively rule out the mimicking disorder, that would help.
I imagine patients and their doctors may begin by doing the simplest, least invasive test first (such as a blood test, if available). But if that blood test comes back negative, it would help to know if that doctor/patient should also pursue the more invasive testing to truly rule out the mimic. Some of these mimicking disorders are so rare that it seems like doctors may not be sure if the more invasive tests/procedures are needed after the initial blood test is done.
If at all possible, if you know of specific laboratories that offer any of these tests (or the specific test name), I think that could help the doctor/patient get through the ‘mimicking’ workups better. From online searches (that the doctor is doing as well), it seems like some of these tests may only be offered by a single testing facility/lab (versus being readily available at any Labcorp/Quest).
PSP is already hard to diagnose as a rare disease without diagnostic tests available. Adding in these ‘mimicking’ disorders that should be considered for doctors/patients not familiar with them (or who are not familiar with the best tests/full workup that’s needed to rule them out) makes it that much harder.
Your work highlighting the PSP and Atypical Parkinsonian ‘mimics’ is very welcome!
I’m working on a list of diagnostic tips and specific treatments for the PSP mimics. But to answer the question in your 4th paragraph: The tests for the PSP mimics are mostly very routine things that the retail labs do all the time. A few of them are genetic tests for very rare conditions, so genetic reference labs would be needed for those. But generally, those genetic mimics are actually easy for a movement disorders specialist to distinguish from PSP without the test.
Thank you Dr. Globe for the informative article. Would love to know more about the conditions which are hard to differentiate with differential diagnosis based on other symptoms. Especially, I am interested knowing Parkinsons with upgaze palsy vs PSP differential diagnosis ( since that’s the one with three asterisk under degenerative).
On the other point, not everyone around the world has easy access to the labs / tests to rule out other rare mimicking conditions and usually neurologist or movement disorder specialist go by observing progression for some longer duration before inclining towards the diagnosis. It would be nice to know any mimicking treatable conditions that should be eliminated as knowing that in later stage might not be helpful.
Good point, Abhay, and it’s true even where those lab tests are readily available. All too often, neurologists are not comfortable diagnosing PSP, or even informing the patient/family of that possibility, until a year or more later, by which time the signs are more obvious. In the post I’m preparing on how to separate PSP from its mimics, I’ll include information that would apply earlier in the disease course. I still don’t have that holy grail of full sensitivity and specificity, however.