Progressive Supranuclear Palsy

Abstract

Progressive supranuclear palsy (PSP) is a neurodegenerative disease that was first described approximately 50 years ago in 1964. When first described, PSP was thought to have a unique clinical presentation characterised by loss of balance leading to early falls, slowness of movements, stiffness of muscles and loss of the ability to voluntarily move the eyes up and down. Subsequently, it has been recognised that patients who have died and have shown microscopic changes in the brain consistent with PSP had other clinical presentations not involving balance, falls or eye movement problems. The term PSP is, therefore, now best reserved for pathological diagnosis. There have been numerous advances in our understanding of PSP, including the fact that patients with PSP can have many different clinical presentations. In this review, we will focus on the pathological, clinical, neuroimaging and genetic characteristics of PSP.

Key Concepts

  • Progressive supranuclear palsy (PSP) is a pathological diagnosis.
  • The cause of PSP is unknown but is thought to be related to abnormal hyperphosphorylated 4R tau.
  • PSP can present as one of many different clinical syndromes.
  • Impaired balance with early falls and vertical eye movement problems are highly predictive of PSP pathology.
  • Atrophy of the premotor cortex, midbrain and superior cerebellar peduncle are the main MRI findings in PSP.
  • There is some evidence that PSP could have genetic underpinnings.

Keywords: supranuclear; tau; tufted astrocytes; pimple sign; midbrain; superior cerebellar peduncle; apraxia of speech; corticobasal syndrome

Figure 1. Facial characteristics of a patient with autopsy‐confirmed PSP. Note the high arching of the eyebrows.
Figure 2. MRI findings in PSP. Left panel demonstrates midbrain atrophy resulting in the hummingbird sign, in which the brainstem takes on the appearance of a hummingbird. Right panel shows small superior cerebellar peduncles (arrows).
Figure 3. 18F‐fluorodeoxyglucose (FDG) PET in PSP. Note the bright signal (red spot) in the midbrain demonstrating strikingly decreased glucose uptake. This FDG finding is known as the pimple sign of PSP.
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Further Reading

Dickson D and Weller R (eds) (2011) Progressive supranuclear palsy and corticobasal degeneration. In: Neurodegeneration: the Molecular Pathology of Dementia and Movement Disorders, pp. 74–89. Hoboken: Wiley‐Blackwell.

Golbe L and Ohman‐Strickland P (2007) A clinical rating scale for progressive supranuclear palsy. Brain 130: 1552–1565.

Litvan I (2005) Atypical Parkinsonian Disorders: Clinical and Research Aspects. Totowa: Humana Press.

Morris H (2010) Progressive supranuclear palsy. In: Schapira A , Lange A and Fahn S , (eds). Movement Disorders IV. Vol. 35. Philadelphia: Sanders Elsevier.

Whitwell JL and Josephs KA (2013) Tauopathies. In: Tuite P and Dagher A , (eds). Magnetic Resonance Imaging in Movement Disorders: a Guide for Clinicians and Scientists, pp. 147–166. Cambridge: Cambridge University Press.

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Josephs, Keith A(Mar 2015) Progressive Supranuclear Palsy. In: eLS. John Wiley & Sons Ltd, Chichester. http://www.els.net [doi: 10.1002/9780470015902.a0025798]