Brain Advance Access originally published online on April 2, 2008
Brain 2008 131(5):1362-1372; doi:10.1093/brain/awn065
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Clinical outcomes of progressive supranuclear palsy and multiple system atrophy
1Reta Lila Weston Institute of Neurological Studies, Institute of Neurology, 2Queen Square Brain Bank for Neurological Disorders and Institute of Neurology, 3Sara Koe PSP Research Centre, Institute of Neurology, University College London, London, UK, 4Faculty of Medicine (Neuroscience), Monash University (Alfred Hospital Campus) and 5Department of Neurosciences, Monash Medical Centre, Melbourne, Australia
Correspondence to: Professor Andrew J. Lees, Reta Lila Weston Institute of Neurological Studies, UCL, 1 Wakefield Street, London, WC1N 1PJ, UK E-mail: alees{at}ion.ucl.ac.uk
Prognostic predictors have not been defined for progressive supranuclear palsy (PSP) and multiple system atrophy (MSA). Subtypes of both disorders have been proposed on the basis of early clinical features. We performed a retrospective chart review to investigate the natural history of pathologically confirmed cases of PSP and MSA. Survival data and several clinically relevant milestones, namely: frequent falling, cognitive disability, unintelligible speech, severe dysphagia, dependence on wheelchair for mobility, the use of urinary catheters and placement in residential care were determined. On the basis of early symptoms, we subdivided cases with PSP into ‘Richardson's syndrome’ (RS) and ‘PSP-parkinsonism’ (PSP-P). Cases of MSA were subdivided according to the presence or absence of early autonomic failure. Sixty-nine (62.7%) of the 110 PSP cases were classified as RS and 29 (26.4%) as PSP-P. Of the 83 cases of MSA, 42 (53.2%) had autonomic failure within 2 years of disease onset. Patients with PSP had an older age of onset (P < 0.001), but similar disease duration to those with MSA. Patients with PSP reached their first clinical milestone earlier than patients with MSA (P < 0.001). Regular falls (P < 0.001), unintelligible speech (P = 0.04) and cognitive impairment (P = 0.03) also occurred earlier in PSP than in MSA. In PSP an RS phenotype, male gender, older age of onset and a short interval from disease onset to reaching the first clinical milestone were all independent predictors of shorter disease duration to death. Patients with RS also reached clinical milestones after a shorter interval from disease onset, compared to patients with PSP-P. In MSA early autonomic failure, female gender, older age of onset, a short interval from disease onset to reaching the first clinical milestone and not being admitted to residential care were independent factors predicting shorter disease duration until death. The time to the first clinical milestone is a useful prognostic predictor for survival. We confirm that RS had a less favourable course than PSP-P, and that early autonomic failure in MSA is associated with shorter survival.
Key Words: multiple system atrophy; progressive supranuclear palsy; natural history
Abbreviations: MSA, multiple system atrophy; MSA-C, MSA-cerebellar; MSA-P, MSA-parkinsonian; PD, Parkinson's disease; PEG, percutaneous endoscopic gastrostomy; PSP, progressive supranuclear palsy; PSP-P, PSP-parkinsonism; QSBB, Queen Square Brain Bank for Neurological Disorders; RS, Richardson's syndrome
Received December 10, 2007. Revised February 29, 2008. Accepted March 7, 2008.