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

Chen AL, Riley DE, King SA, Joshi AC, Serra A, Liao K, Cohen ML, Otero-Millan J, Martinez-Conde S, Strupp M, Leigh RJ - Front Neurol (2010)

Bottom Line: 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.

View Article: PubMed Central - PubMed

Affiliation: Veterans Affairs Medical Center, University Hospitals Case Medical Center Cleveland, OH, USA.

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.

No MeSH data available.


Related in: MedlinePlus

Peak velocity–amplitude relationship of vertical saccades (A) and horizontal saccades (B) made by control subjects (CS) and PSP patients. (A) Upward and downward power fits calculated for all vertical saccades made by 17 PSP patients for whom R2 > 0.7. Fit, 5 and 95% prediction interval (PI) for all CS saccades are shown. Most of the faster downward saccades were made by one patient with 1.5 year disease duration. (B) Horizontal saccades made by PSP patients were slower than those made by CS (with no left-right asymmetry), but slowing was less marked than for vertical saccades. (C) Box-plot comparison of K-values for controls’ and patients’ vertical saccade power fits. Intragroup differences are not significant, but the difference between controls’ K-values and patients’ K-values is (p < 0.001). (D) Comparison of L-values for controls’ and patients’ vertical saccade power fits. Only the intergroup L was found to be different (p = 0.013). Box-plot percentiles are shown at right.
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Figure 3: Peak velocity–amplitude relationship of vertical saccades (A) and horizontal saccades (B) made by control subjects (CS) and PSP patients. (A) Upward and downward power fits calculated for all vertical saccades made by 17 PSP patients for whom R2 > 0.7. Fit, 5 and 95% prediction interval (PI) for all CS saccades are shown. Most of the faster downward saccades were made by one patient with 1.5 year disease duration. (B) Horizontal saccades made by PSP patients were slower than those made by CS (with no left-right asymmetry), but slowing was less marked than for vertical saccades. (C) Box-plot comparison of K-values for controls’ and patients’ vertical saccade power fits. Intragroup differences are not significant, but the difference between controls’ K-values and patients’ K-values is (p < 0.001). (D) Comparison of L-values for controls’ and patients’ vertical saccade power fits. Only the intergroup L was found to be different (p = 0.013). Box-plot percentiles are shown at right.

Mentions: We conducted a paired comparison of the values of the terms in Eq. 1, describing the peak velocity/amplitude relationship of upward and downward saccades made by control subjects and 17 PSP patients with curve fits R2 > 0.7. Figure 3A displays 5 and 95% prediction intervals for 10 control subjects based on all 1,856 of their vertical saccades (nup = 1020, ndown = 836), since paired t-tests detected no differences between upward and downward K- and L-values (p = 0.635 and 0.459). Figure 3A also shows all upward (n = 990) and downward (n = 805) saccades made by 17 PSP patients. For patients, paired t-tests showed no difference for Kup versus Kdown (p = 0.920) or Lup versus Ldown (p = 0.128). Both upward and downward saccades made by patients were slower than those made by age-matched control subjects: mean K-values were 50.161 for patients and 73.583 for controls (p < 0.001); the median L-value was 0.445 for patients and 0.529 for controls (p = 0.013), see Figures 3C,D. We also compared peak velocity/amplitude relationships for centripetal versus centrifugal saccades in the upper and lower hemifields of movement using ANOVA on ranks, and found no difference between any group (p = 0.781).


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

Chen AL, Riley DE, King SA, Joshi AC, Serra A, Liao K, Cohen ML, Otero-Millan J, Martinez-Conde S, Strupp M, Leigh RJ - Front Neurol (2010)

Peak velocity–amplitude relationship of vertical saccades (A) and horizontal saccades (B) made by control subjects (CS) and PSP patients. (A) Upward and downward power fits calculated for all vertical saccades made by 17 PSP patients for whom R2 > 0.7. Fit, 5 and 95% prediction interval (PI) for all CS saccades are shown. Most of the faster downward saccades were made by one patient with 1.5 year disease duration. (B) Horizontal saccades made by PSP patients were slower than those made by CS (with no left-right asymmetry), but slowing was less marked than for vertical saccades. (C) Box-plot comparison of K-values for controls’ and patients’ vertical saccade power fits. Intragroup differences are not significant, but the difference between controls’ K-values and patients’ K-values is (p < 0.001). (D) Comparison of L-values for controls’ and patients’ vertical saccade power fits. Only the intergroup L was found to be different (p = 0.013). Box-plot percentiles are shown at right.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
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Figure 3: Peak velocity–amplitude relationship of vertical saccades (A) and horizontal saccades (B) made by control subjects (CS) and PSP patients. (A) Upward and downward power fits calculated for all vertical saccades made by 17 PSP patients for whom R2 > 0.7. Fit, 5 and 95% prediction interval (PI) for all CS saccades are shown. Most of the faster downward saccades were made by one patient with 1.5 year disease duration. (B) Horizontal saccades made by PSP patients were slower than those made by CS (with no left-right asymmetry), but slowing was less marked than for vertical saccades. (C) Box-plot comparison of K-values for controls’ and patients’ vertical saccade power fits. Intragroup differences are not significant, but the difference between controls’ K-values and patients’ K-values is (p < 0.001). (D) Comparison of L-values for controls’ and patients’ vertical saccade power fits. Only the intergroup L was found to be different (p = 0.013). Box-plot percentiles are shown at right.
Mentions: We conducted a paired comparison of the values of the terms in Eq. 1, describing the peak velocity/amplitude relationship of upward and downward saccades made by control subjects and 17 PSP patients with curve fits R2 > 0.7. Figure 3A displays 5 and 95% prediction intervals for 10 control subjects based on all 1,856 of their vertical saccades (nup = 1020, ndown = 836), since paired t-tests detected no differences between upward and downward K- and L-values (p = 0.635 and 0.459). Figure 3A also shows all upward (n = 990) and downward (n = 805) saccades made by 17 PSP patients. For patients, paired t-tests showed no difference for Kup versus Kdown (p = 0.920) or Lup versus Ldown (p = 0.128). Both upward and downward saccades made by patients were slower than those made by age-matched control subjects: mean K-values were 50.161 for patients and 73.583 for controls (p < 0.001); the median L-value was 0.445 for patients and 0.529 for controls (p = 0.013), see Figures 3C,D. We also compared peak velocity/amplitude relationships for centripetal versus centrifugal saccades in the upper and lower hemifields of movement using ANOVA on ranks, and found no difference between any group (p = 0.781).

Bottom Line: 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.

View Article: PubMed Central - PubMed

Affiliation: Veterans Affairs Medical Center, University Hospitals Case Medical Center Cleveland, OH, USA.

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.

No MeSH data available.


Related in: MedlinePlus