A new definition of PSP

When you design a research project in PSP, it’s important to make sure that everyone in the subject group with PSP in fact has PSP. Otherwise, you degrade the statistical power of the trial to detect any benefit of the treatment. The standard diagnostic criteria for PSP (called the “NINDS-SPSP Criteria” and spearheaded by Irene Litvan, MD, now of UCSD) were published in 1996 and have worked well for that purpose; Their positive predictive value (the fraction of patients satisfying the criteria who actually have PSP) and specificity (the fraction of those without PSP who fail to satisfy the criteria) are close to 100%.
But as we now enter the new era of trials of experimental neuroprotective treatment for PSP, we would like to diagnose the disease at an earlier stage, when such interventions are most likely to be effective, and the NINDS-SPSP Criteria don’t do that so well, with a sensitivity of about 80% overall, certainly lower in early cases. Another shortcoming is that the various phenotypes of PSP that have been described since 2005 won’t in many cases satisfy the criteria, which were designed for the “original flavor,” now called PSP-Richardson’s syndrome.
So time has marched on and we need a new set of criteria. Günter Höglinger, MD, Professor at the German Center for Neurodegenerative Disorders in Munich and probably the world’s leading clinical researcher in PSP, organized an international effort to revise the criteria. I’m privileged to serve on the four-person Steering Committee. A year ago we started to hash things out by email and conference calls, using the published articles on clinical features of PSP that use either autopsy or the NINDS-SPSP Criteria as a gold standard. The group, comprising 33 people from 11 countries, met in Munich on March 9 and 10 to turn our rough draft into a final version suitable for submission to a journal for peer review.
The new criteria recognize the various phenotypes of PSP. They are PSP-Richardson syndrome (about 55% of all PSP), PSP-parkinsonism (30%), PSP-frontal dementia (5%), PSP-ocular motor (1%), PSP- pure akinesia with gait freezing (1%), PSP-corticobasal syndrome (1%), PSP-progressive non-fluent aphasia (1%), and PSP-cerebellar (<1%). The remaining few percent are combinations of these or still-unrecognized forms.
The new criteria also delineate various “oligosymptomatic” or “prodromal” (the wording remains unsettled) forms, which may or may not develop into one of the diagnosable phenotypes. For example, there is now evidence that someone in the PSP age group with gradually progressive gait freezing for several years and a normal MRI, even without other abnormalities, will almost always prove to have PSP. The same is true for someone with bilateral rigidity and bradykinesia who fails to respond to levodopa and has some sort of nonspecific, undiagnosable visual symptoms or dizziness. Neither of these patients would satisfy the proposed new criteria for any of the PSP phenotypes, but they may still be worth identifying for inclusion in a longitudinal cohort study of people who are at risk of developing PSP. Our new criteria do that.
I’ll keep you updated.

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5 thoughts on “A new definition of PSP

  1. Very interesting blog! The first symptoms that lead later to the diagnosis of PSP for my wife were identified more than 10 years ago (micrography). Since then she has developed many more symptoms all very related to PSP: loss of balance (specialy rear movement) vision, elocution, respiration etc…However the evolution has been so slow that some neurologists took a long time before being finally convinced that it was indeed PSP.
    Among the various types of PSP that you list, are there some that evolve much slower than others? It seems that the case of my wife is realy abnormal; she is still capable of doing treadmill exercise every day (under supervision)! Her character has changed but her abilities to reason and remember are intact. She is now 61.
    PS Incredibly, my brother has also been diagnosed with PSP but with a more normal evolution. 4 years after the first symptoms, he is practically unable to move by himself!

  2. It’s true that some people with PSP can have a much slower course. This is generally true for those with the PSP-parkinsonism type or with younger onset age. Another possibility is that the real diagnosis is something other than PSP.

  3. In the case of my sister, she starts with a well-defined PD but with a high rate of falling.
    Of course the psychologist, occupational therapist, the physiatric and the psychiatric MD, diagnostics attributes the falling to my sister’s deny of the disease. It is a reasonable hypothesis.

    Actually, she was diagnosticated at 63 years old, she is now, 72.
    At the beginning, she had overcome the problems of voice with a music teacher, the anxiety with meditation, the freezing of her right side with swimming and always a physiatric assistance together with drugs by a neurologist. In the last year, she develops a progressive functional blindness that was first diagnosticated as a palpebral spasm. Botox application around the ocular orbit was not successful. In the near future, the neurologist will try with botox in the ocular elevator muscle. Nevertheless, she changes her mood to a more impulsive attitude, frequently falling, and also afraid of falling, to become completely blind, etc. I have asked for a continued psychological assistance and not during a month. I understand she is in front of a new step of her progressive illness and she needs to adapt her attitudes to blindness. Could you advise my of any other action to take?

    Could be that a state of very high labor stress triggered her disease, with some genetics predisposition?

    Sorry for my English. I live in Buenos Aires Argentina. I am a Physics Ph.D., and my sister has been working until 70 at State Education Administration as a Project Leader. So, it is not a matter of lower education as I have read in a post.

    Thank you in advance

    eforlerer@gmail.com

  4. Hi Elena, my Dad has had PSP for over 10 years, was diagnosed 2 years ago, and he’s now bedridden. Perhaps not in all cases, but in many, PSP damages the part of the brain that controls impulsive, risky behavior. It certainly happened that way for my father and caused many falls, usually backwards as is another characteristic of the dreaded psp. Just thought I’d throw that in there. It’s not so much their mood changing as it is that particular place in the brain being affected.

    • The evolution of my sister’s disease, supposed to be a PSP Richardson, is slower than in your father’s case but is progressive. The only thing I can do is understanding the behavioral signs, have a strong prevention attitude and be a companion. Warm regards. Elena

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