Two distinct types of PSP – RS and PSP-parkinsonism

Here’s the citation to a very important paper published recently on progressive supranuclear palsy (PSP):

Brain. 2005 Jun;128(Pt 6):1247-58. Epub 2005 Mar 23. 
Characteristics of two distinct clinical phenotypes in pathologically proven progressive supranuclear palsy: Richardson’s syndrome and PSP-parkinsonism.
Williams DR, de Silva R, Paviour DC, Pittman A, Watt HC, Kilford L, Holton JL, Revesz T, Lees AJ.
The Queen Square Brain Bank for Neurological Disorders, University College London, UK.

Dr. David Williams and others from The Queen Square Brain Bank in London examined the brains and clinical records of 103 people with autopsy-confirmed PSP.  They discovered two key clinical types of PSP:  Richardson’s Syndrome and PSP-parkinsonism.

The authors described Richardson’s Syndrome (RS) as follows:

“The core clinical features of PSP appears to be bradykinesia, rigidity and postural instability, and are almost always present later in the disease.  Together with the supranuclear vertical ophthalmoplegia, dementia, dysarthria and pseudobulbar palsy, they form the classic features of PSP.  When these features appear in the first 2 years, a diagnosis of RS is most likely.”

The authors described the PSP-parkinsonism type as follows:

“The features which most clearly differentiate this syndrome from RS appear to be an asymmetric onset, extra-axial dystonia, tremor and benefit from levodopa.  Early bradykinesia appears to be essential for the diagnosis, but does not adequately differentiate it from RS, especially later in the disease course.  Disease duration in PSP-P is significantly longer than in RS, and to our knowledge exceeds median survival in all clinicopathological PSP case series.”

Here’s the abstract to this important paper:  (broken into paragraphs)

“The clinical diagnosis of progressive supranuclear palsy (PSP) relies on the identification of characteristic signs and symptoms. A proportion of pathologically diagnosed cases do not develop these classic features, prove difficult to diagnose during life and are considered as atypical PSP. The aim of this study was to examine the apparent clinical dichotomy between typical and atypical PSP, and to compare the biochemical and genetic characteristics of these groups.

In 103 consecutive cases of pathologically confirmed PSP, we have identified two clinical phenotypes by factor analysis which we have named Richardson’s syndrome (RS) and PSP-parkinsonism (PSP-P). Cases of RS syndrome made up 54% of all cases, and were characterized by the early onset of postural instability and falls, supranuclear vertical gaze palsy and cognitive dysfunction. A second group of 33 (32%) were characterized by asymmetric onset, tremor, a moderate initial therapeutic response to levodopa and were frequently confused with Parkinson’s disease (PSP-P). Fourteen cases (14%) could not be separated according to these criteria. In RS, two-thirds of cases were men, whereas the sex distribution in PSP-P was even. Disease duration in RS was significantly shorter (5.9 versus 9.1 years, P < 0.001) and age at death earlier (72.1 versus 75.5 years, P = 0.01) than in PSP-P.

The isoform composition of insoluble tangle-tau isolated from the basal pons also differed significantly. In RS, the mean four-repeat:three-repeat tau ratio was 2.84 and in PSP-P it was 1.63 (P < 0.003). The effect of the H1,H1 PSP susceptibility genotype appeared stronger in RS than in PSP-P (odds ratio 13.2 versus 4.5). The difference in genotype frequencies between the clinical subgroups was not significant. There were no differences in apolipoprotein E genotypes.

The classic clinical description of PSP, which includes supranuclear gaze palsy, early falls and dementia, does not adequately describe one-third of cases in this series of pathologically confirmed cases. We propose that PSP-P represents a second discrete clinical phenotype that needs to be clinically distinguished from classical PSP (RS). The different tau isoform deposition in the basal pons suggests that this may ultimately prove to be a discrete nosological entity.”

From my reading, the PSP-parkinsonism type of PSP looks like Parkinson’s Disease and may look like MSA, specifically the parkinsonism type (MSA-P).

According to the full article, some people with PSP actually had a response to levodopa therapy!  Do the diagnostic criteria need to be changed to accommodate this finding?

Robin


Update from 2007:

This important paper is now available online at no cost.

Here’s the direct link to the Brain ’05 article:

brain.oxfordjournals.org/cgi/reprint/128/6/1247

And I think the commentary is worth reading too:

brain.oxfordjournals.org/cgi/reprint/128/6/1235