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Front. Neurol., 03 December 2010 |

The disturbance of gaze in progressive supranuclear palsy: implications for pathogenesis

Athena L. Chen1, David E. Riley2, Susan A. King1, Anand C. Joshi2, Alessandro Serra1,2, Ke Liao1, Mark L. Cohen3, Jorge Otero-Millan4, Susana Martinez-Conde4, Michael Strupp5 and R. John Leigh1,2*
  • 1 Veterans Affairs Medical Center, University Hospitals Case Medical Center, Cleveland, OH, USA
  • 2 Neurological Institute, University Hospitals Case Medical Center, Cleveland, OH, USA
  • 3 Department of Pathology, University Hospitals Case Medical Center, Cleveland, OH, USA
  • 4 Barrow Neurological Institute, Phoenix, AZ, USA
  • 5 Department of Neurology and IFB-LMU, University of Munich, Munich, Germany

Progressive supranuclear palsy (PSP) is a disease of later life that is currently regarded as a form of neurodegenerative tauopathy. Disturbance of gaze is a cardinal clinical feature of PSP that often helps clinicians to establish the diagnosis. Since the neurobiology of gaze control is now well understood, it is possible to use eye movements as investigational tools to understand aspects of the pathogenesis of PSP. In this review, we summarize each disorder of gaze control that occurs in PSP, drawing on our studies of 50 patients, and on reports from other laboratories that have measured the disturbances of eye movements. When these gaze disorders are approached by considering each functional class of eye movements and its neurobiological basis, a distinct pattern of eye movement deficits emerges that provides insight into the pathogenesis of PSP. Although some aspects of all forms of eye movements are affected in PSP, the predominant defects concern vertical saccades (slow and hypometric, both up and down), impaired vergence, and inability to modulate the linear vestibulo-ocular reflex appropriately for viewing distance. These vertical and vergence eye movements habitually work in concert to enable visuomotor skills that are important during locomotion with the hands free. Taken with the prominent early feature of falls, these findings suggest that PSP tauopathy impairs a recently evolved neural system concerned with bipedal locomotion in an erect posture and frequent gaze shifts between the distant environment and proximate hands. This approach provides a conceptual framework that can be used to address the nosological challenge posed by overlapping clinical and neuropathological features of neurodegenerative tauopathies.

Keywords: saccades, vergence, vestibular, parkinsonian disorders, tauopathy

Citation: Chen AL, Riley DE, King SA, Joshi AC, Serra A, Liao K, Cohen ML, Otero-Millan J, Martinez-Conde S, Strupp M and Leigh RJ (2010) The disturbance of gaze in progressive supranuclear palsy: implications for pathogenesis. Front. Neur. 1:147. doi: 10.3389/fneur.2010.00147

Received: 14 September 2010; Accepted: 03 November 2010;
Published online: 03 December 2010.

Edited by:

Adolfo M. Bronstein, Imperial College London, UK

Reviewed by:

Dominik Straumann, University Hospital Zurich, Switzerland
Alexandre Bisdorff, Centre Hospitalier Emile Mayrisch, Luxembourg

Copyright: © 2010 Chen, Riley, King, Joshi, Serra, Liao, Cohen, Otero-Millan, Martinez-Conde, Strupp and Leigh. This is an open-access article subject to an exclusive license agreement between the authors and the Frontiers Research Foundation, which permits unrestricted use, distribution, and reproduction in any medium, provided the original authors and source are credited.

*Correspondence: R. John Leigh, Department of Neurology, University Hospitals, 11100 Euclid Avenue, Cleveland, OH 44106-5040, USA. e-mail: