The genetic and clinico-pathological profile of early-onset progressive supranuclear palsy.
Mov Disord
; 34(9): 1307-1314, 2019 09.
Article
em En
| MEDLINE
| ID: mdl-31299107
ABSTRACT
BACKGROUND:
Studies on early-onset presentations of progressive supranuclear palsy (PSP) have been limited to those where a rare monogenic cause has been identified. Here, we have defined early-onset PSP (EOPSP) and investigated its genetic and clinico-pathological profile in comparison with late-onset PSP (LOPSP) and Parkinson's disease (PD).METHODS:
We included subjects from the Queen Square Brain Bank, PROSPECT-UK study, and Tracking Parkinson's study. Group comparisons of data were made using Welch's t-test and Kruskal-Wallis analysis of variance. EOPSP was defined as the youngest decile of motor age at onset (≤55 years) in the Queen Square Brain Bank PSP case series.RESULTS:
We identified 33 EOPSP, 328 LOPSP, and 2000 PD subjects. The early clinical features of EOPSP usually involve limb parkinsonism and gait freezing, with 50% of cases initially misdiagnosed as having PD. We found that an initial clinical diagnosis of EOPSP had lower diagnostic sensitivity (33%) and positive predictive value (38%) in comparison with LOPSP (80% and 76%) using a postmortem diagnosis of PSP as the gold standard. 3/33 (9%) of the EOPSP group had an underlying monogenic cause. Using a PSP genetic risk score (GRS), we showed that the genetic risk burden in the EOPSP (mean z-score, 0.59) and LOPSP (mean z-score, 0.48) groups was significantly higher (P < 0.05) when compared with the PD group (mean z-score, -0.08).CONCLUSIONS:
The initial clinical profile of EOPSP is often PD-like. At the group level, a PSP GRS was able to differentiate EOPSP from PD, and this may be helpful in future diagnostic algorithms. © 2019 The Authors. Movement Disorders published by Wiley Periodicals, Inc. on behalf of International Parkinson and Movement Disorder Society.Palavras-chave
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Paralisia Supranuclear Progressiva
Tipo de estudo:
Diagnostic_studies
/
Prognostic_studies
Limite:
Adult
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Aged
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Aged80
/
Female
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Humans
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Male
/
Middle aged
Idioma:
En
Ano de publicação:
2019
Tipo de documento:
Article