The PSP Association

Researchers Dr Uma Nath (Clinical Research Fellow)
Supervisor Professor David Burn

Institution Newcastle upon Tyne University and Royal Victoria Infirmary, Newcastle upon Tyne

Duration 2 years
Start Sept 1998 End Sept 2000

Grant £93,000

Aim of research
• To estimate the number of people in the UK suffering from PSP
• To gain an idea of the level of under-ascertainment (missed or unreported cases) of PSP in the UK
• To describe the symptoms and physical signs in PSP and identify any factors that could predict the course of the disease
• To estimate the mortality of PSP
• To determine the quality of death certification in patients with PSP

About the research
This was an epidemiological study concerned with establishing how many cases of PSP there are in the UK at a given time and how many are potentially missed.

There were three strands to this work through which we built up a picture of the numbers of cases of PSP at national, regional and community levels. Nationally, we asked neurologists across the UK to send us details of cases of PSP ("passive" national case finding). Records were reviewed to see if they met the NINDS-SPSP criteria for PSP. Regionally, we actively sought cases across the North East of England using multiple methods such as requesting cases from a wide variety of physicians not just neurologists. We also reviewed clinic letters from all physicians; looked at Parkinson's Nurse databases; PEG (feeding) tube registers and hospital in-patient coding systems ("active" regional case finding). Patient records were reviewed. Patients were also clinically assessed where possible.

For the community study, which took place in 35 GP practices in and around Newcastle upon Tyne, all GP records were screened to identify records of patients with parkinsonism or who had tried levodopa. The second stage of this process involved identifying those who had falls or did not respond to levodopa. These patients were clinically assessed by structured interview to see whether they met criteria for PSP.

Information was also gathered on previous diagnoses including GP diagnosis; first symptom, how long it took before each symptom arose, referral pattern, response to treatment and date of death. This data was collected in a specially constructed database with a "tracking" system so that the way each patient was identified could be audited. In this way the relative efficiency of using different methods of case identification could be compared.

Findings
In the national study, 577 cases of PSP were identified. This gave a prevalence of 1 case per 100 000. The regional study identified 80 cases of PSP giving a prevalence estimate of 2.4 cases per 100 000. In the more detailed community study, 17 cases of PSP were identified giving a prevalence of 5 cases per 100 000. Seven of the 17 cases had not been previously diagnosed with PSP.

This study demonstrated clearly that the disorder was more common than previously thought and that misdiagnosis was not uncommon.

There was a 20 fold variation in prevalence depending on the methods of case finding.

Records based diagnosis identified 187 cases of PSP. A third of these were examined.

The most common symptoms at onset related to mobility. In those cases examined, double vision occurred in 61%, light sensitivity in 43%, and eyelid problems in 43%.

Sixty-five percent of patients were referred to non neurologists initially and 13% had never seen a neurologist. Cases referred to non neurologists were older than those referred to neurologists.

Older patients, early onset of falls, speech problems or double vision within 1 year or swallowing difficulty within 2 years were associated with poorer survival. Visual symptoms were found to be very disabling - several patients were found to have eyelid problems so severe they were registered blind.

Initial response to levodopa and presence of tremor was found in around a fifth of cases.

Average survival was 5.7 years with speech problems developing at 2 years.

Mortality estimates across England and Wales showed that an average of 90 deaths per year cited PSP on death certificates. Thus a crude annual mortality rate was estimated of 1.77 cases per million. The number of death certificates mentioning PSP rose annually from 1.08 in 1993 to 2.68 per million in 2000. In the analysis of death certificates from the prevalence study, it was shown that 65% of certificates on known PSP patients mentioned the disease. The commonest cause of death was pneumonia.

What does the outcome of this research mean for people with PSP?
This is a landmark study and provided for the first time ever an estimate of the number of cases of PSP in the UK.

To have an estimate is crucial as without it, it is impossible for the government to provide adequate service provision to meet the needs of people with PSP.

The study showed that the accuracy of estimates of disease frequency depends on how the studies are conducted. It also highlighted the large number of cases of PSP where the diagnosis is missed or delayed and how the early manifestations of PSP lead to potential referral to a wide variety of specialists.

Early behavioural or cognitive (memory) problems were found in 15% of patients and could be misinterpreted as depression. The study identified the high frequency and functional importance of eyelid apraxia (difficulty in opening eyes), a potentially treatable aspect of PSP.

The study indicated that older patients and early development of visual problems is associated with poorer survival. The presence of a symptom seems to be less important than when it develops in terms of survival.

Whilst death certification for PSP was found to be improving it is still suboptimal.

Publications arising from the work
U Nath, Y Ben Shlomo, RG Thomson, HR Morris, NW Wood, AJ Lees, DJ Burn. The prevalence of progressive supranuclear palsy (Steele Richardson Olszewski syndrome) in the UK
Brain 2001, 124, 1438-1449.

U Nath, Y Ben-Shlomo, RG Thomson, HR Morris, NW Wood, AJ Lees, DJ Burn. Estimation of case underascertainment in a UK-based prevalence study (abstract)
International Epidemiological Association and Society of Social Medicine Feb 2001

U Nath, Y Ben Shlomo, RG Thomson, AJ Lees, DJ Burn. Clinical features and natural history of progressive supranuclear palsy; a clinical cohort study. Neurology 2003; 60:910-916.

U Nath, RG Thomson, Y Ben Shlomo, AJ Lees, C Rooney and DJ Burn. Population based mortality and quality of death certification in progressive supranuclear palsy. J Neurol Neurosurg Psych 2005;76:498-502.

National/international presentations given on this work
Regional Branch meeting of British Geriatrics Society 1999
PSP - creation of a national register and in-depth regional study

Poster presentation to Association of British Neurologists 1999
The Russian Doll Design; an epidemiological study in PSP

Parkinson's Disease Interest Group meeting 1999
Epidemiology of PSP in the UK

NoReN (Northern primary Care Research Network) Study day 1999
Epidemiology and differential diagnosis of PSP

Bangalore, India 2000
The differential diagnosis of PSP
Glaxo Neurological Centre Conference on PSP CBD and MSA 2000

Epidemiology of PSP in the UK
Platform presentation to 52nd meeting of American Academy of Neurology 2000

Epidemiology of PSP ;The Russian Doll Approach
Platform presentation to Association of British Neurologists 2000

Clinical features of PSP in the UK
Poster presentation to World congress of Neurology 2001

Natural History of PSP
Association of Physicians of Region no 1 2001

Clinical features of PSP in the UK
Platform presentation to 53rd meeting of American Academy of Neurology 2001

Clinical features of PSP
Platform presentation to Association of British Neurologists 2001

Poster presentation, Neurosciences at Newcastle symposium, December 2001
PSP: clinical features and disease course

PSP Symposium 2002 Bristol
Mortality in PSP

Poster presentation Movement Disorder Conference Miami November 2002
‘The differential diagnosis of PSP'

Awards and prizes received for work conducted under this grant
Charles Symonds Prize (best platform presentation to Association of British Neurologists 2001)
Liversedge Prize (best platform presentation to North East Association of Neurologists 2001)
PSP Association award for contribution to research in PSP 1999-2000 MD thesis with commendation for PSP study

How has the grant you received influenced your future career and research direction?

Dr Uma Nath says,
"This research established my interest in the extrapyramidal disorders. I now run a Movement Disorders clinic in Sunderland and maintain a special interest in the management of PSP patients. As part of the study I traveled across the North East and conducted numerous workshops in PSP diagnosis with over 100 regional physicians, ophthalmologists and neurologists. This raised the profile of the disorder regionally which remains to this day.

It was a pleasure and privilege to be a PSP Association Clinical Research Fellow and to work with The PSP Association. This necessary and much needed work would not have been funded without the Association's support. Its mode of supporting Research Fellows is exemplary. I wish the Association all the best for the future. The fund of goodwill the Association has generated through it supporting Research Fellows and by conducting international workshops has raised the research profile and stimulated active interest in this disorder.