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

David E Riley,Susana Martinez-Conde,Athena L Chen,Anand C Joshi,Mark L Cohen,Alessandro Serra,Michael Strupp,Ke Liao,R John Leigh,Jorge Otero-Millan,Susan A King

doi:10.3389/fneur.2010.00147

Abstract

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.

Highlights

Since its original description (Steele et al, 1964), vertical gaze palsy has been recognized as a defining characteristic of progressive supranuclear palsy (PSP) that helps clinicians differentiate this disease from other parkinsonian disorders
It is apparent that saccades made by the PSP patient are smaller and slower than those made by the control subject
Few studies have measured vergence combined with vertical saccades, such as occurs when attention is switched between a handheld object and a distant target, but we have found that such combined vergence–saccade movements are smaller and slower in PSP patients compared with control subjects (Kitthaweesin et al, 2002)

Summary

Introduction

Since its original description (Steele et al, 1964), vertical gaze palsy has been recognized as a defining characteristic of progressive supranuclear palsy (PSP) that helps clinicians differentiate this disease from other parkinsonian disorders. It has been proposed that classic PSP be called Richardson’s syndrome, and be distinguished from mixed presentations These include: (1) PSP-parkinsonism (PSP-P), in which tremor may be present, falls and cognitive changes are not early features, and for which levodopa produces improvement; (2) PSP-corticobasal syndrome (PSP-CBS), in which asymmetric apraxia, cortical sensory loss, dystonia and lack of response to levodopa occur (Ling et al, 2010); (3) pure akinesia (PA) that affects speech, handwriting and gait, in the absence of tremor, limb rigidity or dementia, and levodopa responsiveness; and (4) PSP with progressive non-fluent aphasia (PSP-PNFA), which is distinguished by disturbance of the initiation, timing and flow of speech (Williams and Lees, 2009)

Methods

Results

Conclusion