Clinical-pathological correlates in PSP (and MSA)

This is a terrific little study done comparing brain tissue of 15 PSP cases, 12 MSA cases, 8 PD cases, and 8 healthy controls, and correlating the pathology with clinical variables (age at onset, disease duration, and symptoms).

The study was done in Australia using tissue donated to the Sydney Brain Bank. I say it was a “little” study because the previous clinical-pathological correlation study in MSA and PSP had much larger numbers — 110 PSP cases and 83 MSA cases. That larger Queen Square Brain Bank (UK) study “did not consider the pathological severity of disease or assess pathological correlations to clinical features.” (This is O’Sullivan’s “Clinical outcomes” article published in the journal Brain in 2008.  We have posted about that here.)

The symptoms studied include the:

“presence or absence of…bradykinesia and rigidity, resting tremor, postural instability, response to levodopa (L-dopa) therapy, dementia as indicated from the last Clinical Dementia Rating (CDR) score, early falls (within the first 2 years of onset), supranuclear vertical gaze abnormalities (abnormal or slow vertical gaze and/or supranuclear gaze palsy), dysarthria, dysphagia, postural hypotension, autonomic and urinary dysfunction, and gait ataxia. The severity of parkinsonism was assessed using the last Hoehn and Yahr (H&Y) score prior to death.”

Here’s some key data on the clinical variables:

Age at onset
PSP: 67 years +/- 9 years

Disease duration
PSP: 7 years +/- 4 years

Phenotype (parkinsonian: parkinsonian-plus)
PSP: 5:10

% L-dopa responsive
PSP: 47%

% demented
PSP: 67%
MSA: 0%

% early falls
PSP: 93%

% gaze abnormalities
PSP: 73%

% dysarthria
PSP: 60%

% autonomic dysfunction
PSP: 47%

% gait ataxia
PSP: 40%

The researchers divide cases by phenotype — parkinsonian or parkinsonian-plus. My assumption is that, for PSP, the parkinsonian phenotype is called PSP-Parkinsonism and the parkinsonian-plus phenotype is called RS (Richardson’s Syndrome).

“As expected, response to L-dopa was associated with a parkinsonian phenotype across all groups, although resting tremor was not associated with either phenotype. The presence of supranuclear vertical gaze abnormalities and early falls was associated with a parkinsonian-plus phenotype across groups, although autonomic dysfunction and gait ataxia were not associated with either phenotype.”

I’ve copied the abstract below.



Movement Disorders. 2011 Jan 21.

Clinical correlates of similar pathologies in parkinsonian syndromes.

Song YJ, Huang Y, Halliday GM.
Neuroscience Research Australia and the University of New South Wales, Randwick, New South Wales, Australia.

BACKGROUND: There have been no previous studies assessing the severity of regional atrophy, cell loss and lesion densities between the overlapping conditions of Parkinson’s disease (PD), progressive supranuclear palsy (PSP) and multiple system atrophy (MSA) and relating these pathologies to different clinical features.

METHODS: Clinical indices and basal ganglia, brainstem, and cerebellar pathology from 43 longitudinally studied cases (PD = 8, PSP = 15, MSA = 12, controls = 8) were compared. A point-counting method was used to evaluate subregional volumes, and alpha-synuclein and phospho-tau immunohistochemistry was used to assess pathological inclusions and stage disease severity. Logistic regression analyses were used to identify pathological associations with clinical features.

RESULTS: All PD, PSP, and MSA cases had severe degeneration of the substantia nigra. Clinical features correlated with tissue loss and the severity of inclusion pathologies. Levodopa responsiveness and a lack of resting tremor was associated with preservation of pallidal volume, the presence of gait ataxia was associated with atrophy of the putamen, and the parkinsonian-plus phenotype with early falls and supranuclear vertical gaze abnormalities had more substantial midbrain atrophy and greater inclusion pathology in the caudate nucleus.

DISCUSSION: This is the first study to compare the severity of regional pathologies across parkinsonian conditions. The data show that tissue loss and inclusion densities in certain regions correlate with clinical indices, with regional volume changes likely to be the best indicator of clinical progression of disease.

Copyright © 2011 Movement Disorder Society.

PubMed ID#: 21259341 (see for the abstract only)