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The saccadic and neurological deficits in type 3 Gaucher disease.

Benko W, Ries M, Wiggs EA, Brady RO, Schiffmann R, Fitzgibbon EJ - PLoS ONE (2011)

Bottom Line: We found that patients with type 3 Gaucher disease had a significantly higher regression slope of duration vs amplitude and peak duration vs amplitude compared to healthy controls for both horizontal and vertical saccades.Saccadic latency was significantly increased for horizontal saccades only.Vertical saccade peak duration vs amplitude slope significantly correlated with IQ and with the performance on the Purdue Pegboard but not with the brainstem and somatosensory evoked potentials.

View Article: PubMed Central - PubMed

Affiliation: Developmental and Metabolic Neurology Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland, United States of America.

ABSTRACT

Unlabelled: Our objective was to characterize the saccadic eye movements in patients with type 3 Gaucher disease (chronic neuronopathic) in relationship to neurological and neurophysiological abnormalities. For approximately 4 years, we prospectively followed a cohort of 15 patients with Gaucher type 3, ages 8-28 years, by measuring saccadic eye movements using the scleral search coil method. We found that patients with type 3 Gaucher disease had a significantly higher regression slope of duration vs amplitude and peak duration vs amplitude compared to healthy controls for both horizontal and vertical saccades. Saccadic latency was significantly increased for horizontal saccades only. Downward saccades were more affected than upward saccades. Saccade abnormalities increased over time in some patients reflecting the slowly progressive nature of the disease. Phase plane plots showed individually characteristic patterns of abnormal saccade trajectories. Oculo-manual dexterity scores on the Purdue Pegboard test were low in virtually all patients, even in those with normal cognitive function. Vertical saccade peak duration vs amplitude slope significantly correlated with IQ and with the performance on the Purdue Pegboard but not with the brainstem and somatosensory evoked potentials. We conclude that, in patients with Gaucher disease type 3, saccadic eye movements and oculo-manual dexterity are representative neurological functions for longitudinal studies and can probably be used as endpoints for therapeutic clinical trials.

Trial registration: ClinicalTrials.gov NCT00001289.

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Related in: MedlinePlus

A. Slope of peak duration vs amplitude for vertical vs horizontal saccades.The line is a least squares regression of the data points and has an R2 value of 0.3. This graph suggests there is a tendency for vertical and horizontal saccade performance to track together and the p value for that tendency is <0.005. B. Graph of regression slopes of saccade duration vs amplitude for vertical vs horizontal saccades. Again the least squares regression fit of the data points is shown and has an R2 value of 0.31. The test for relationship has a p<0.005. C. Graph of vertical vs horizontal latencies (data from the last visit). The regression line has an R2 of 0.68 and the test for relationship has p<0.00001.
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pone-0022410-g003: A. Slope of peak duration vs amplitude for vertical vs horizontal saccades.The line is a least squares regression of the data points and has an R2 value of 0.3. This graph suggests there is a tendency for vertical and horizontal saccade performance to track together and the p value for that tendency is <0.005. B. Graph of regression slopes of saccade duration vs amplitude for vertical vs horizontal saccades. Again the least squares regression fit of the data points is shown and has an R2 value of 0.31. The test for relationship has a p<0.005. C. Graph of vertical vs horizontal latencies (data from the last visit). The regression line has an R2 of 0.68 and the test for relationship has p<0.00001.

Mentions: We asked whether patients with more severely affected horizontal saccades would have more severely affected vertical saccade parameters. Graphing the slopes of horizontal vs vertical saccades for duration vs amplitude and peak-duration vs amplitude we found correlation coefficients of 0.31 in both cases (p<0.005, Figure 3A, 3B). The regression of horizontal vs vertical saccade latency had a correlation coefficient of 0.68 (p<0.005, Figure 3C). This suggests that the two systems do tend to track together, both worsening with disease progression. However, the correlation is imperfect, in part because there is a floor effect when the horizontal saccades are very poor and cannot become any worse. For several patients with the longest follow up, we viewed saccadic parameters across time and were unable to demonstrate a consistent decline in follow up visits by looking at the slopes of peak duration vs amplitude for each patient's upward saccades over time (Figure 4). Upward saccades were chosen since these were the least abnormal. Graphing downward and horizontal saccade slopes over time did not demonstrate any consistent pattern of decline (see also below).


The saccadic and neurological deficits in type 3 Gaucher disease.

Benko W, Ries M, Wiggs EA, Brady RO, Schiffmann R, Fitzgibbon EJ - PLoS ONE (2011)

A. Slope of peak duration vs amplitude for vertical vs horizontal saccades.The line is a least squares regression of the data points and has an R2 value of 0.3. This graph suggests there is a tendency for vertical and horizontal saccade performance to track together and the p value for that tendency is <0.005. B. Graph of regression slopes of saccade duration vs amplitude for vertical vs horizontal saccades. Again the least squares regression fit of the data points is shown and has an R2 value of 0.31. The test for relationship has a p<0.005. C. Graph of vertical vs horizontal latencies (data from the last visit). The regression line has an R2 of 0.68 and the test for relationship has p<0.00001.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3140522&req=5

pone-0022410-g003: A. Slope of peak duration vs amplitude for vertical vs horizontal saccades.The line is a least squares regression of the data points and has an R2 value of 0.3. This graph suggests there is a tendency for vertical and horizontal saccade performance to track together and the p value for that tendency is <0.005. B. Graph of regression slopes of saccade duration vs amplitude for vertical vs horizontal saccades. Again the least squares regression fit of the data points is shown and has an R2 value of 0.31. The test for relationship has a p<0.005. C. Graph of vertical vs horizontal latencies (data from the last visit). The regression line has an R2 of 0.68 and the test for relationship has p<0.00001.
Mentions: We asked whether patients with more severely affected horizontal saccades would have more severely affected vertical saccade parameters. Graphing the slopes of horizontal vs vertical saccades for duration vs amplitude and peak-duration vs amplitude we found correlation coefficients of 0.31 in both cases (p<0.005, Figure 3A, 3B). The regression of horizontal vs vertical saccade latency had a correlation coefficient of 0.68 (p<0.005, Figure 3C). This suggests that the two systems do tend to track together, both worsening with disease progression. However, the correlation is imperfect, in part because there is a floor effect when the horizontal saccades are very poor and cannot become any worse. For several patients with the longest follow up, we viewed saccadic parameters across time and were unable to demonstrate a consistent decline in follow up visits by looking at the slopes of peak duration vs amplitude for each patient's upward saccades over time (Figure 4). Upward saccades were chosen since these were the least abnormal. Graphing downward and horizontal saccade slopes over time did not demonstrate any consistent pattern of decline (see also below).

Bottom Line: We found that patients with type 3 Gaucher disease had a significantly higher regression slope of duration vs amplitude and peak duration vs amplitude compared to healthy controls for both horizontal and vertical saccades.Saccadic latency was significantly increased for horizontal saccades only.Vertical saccade peak duration vs amplitude slope significantly correlated with IQ and with the performance on the Purdue Pegboard but not with the brainstem and somatosensory evoked potentials.

View Article: PubMed Central - PubMed

Affiliation: Developmental and Metabolic Neurology Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland, United States of America.

ABSTRACT

Unlabelled: Our objective was to characterize the saccadic eye movements in patients with type 3 Gaucher disease (chronic neuronopathic) in relationship to neurological and neurophysiological abnormalities. For approximately 4 years, we prospectively followed a cohort of 15 patients with Gaucher type 3, ages 8-28 years, by measuring saccadic eye movements using the scleral search coil method. We found that patients with type 3 Gaucher disease had a significantly higher regression slope of duration vs amplitude and peak duration vs amplitude compared to healthy controls for both horizontal and vertical saccades. Saccadic latency was significantly increased for horizontal saccades only. Downward saccades were more affected than upward saccades. Saccade abnormalities increased over time in some patients reflecting the slowly progressive nature of the disease. Phase plane plots showed individually characteristic patterns of abnormal saccade trajectories. Oculo-manual dexterity scores on the Purdue Pegboard test were low in virtually all patients, even in those with normal cognitive function. Vertical saccade peak duration vs amplitude slope significantly correlated with IQ and with the performance on the Purdue Pegboard but not with the brainstem and somatosensory evoked potentials. We conclude that, in patients with Gaucher disease type 3, saccadic eye movements and oculo-manual dexterity are representative neurological functions for longitudinal studies and can probably be used as endpoints for therapeutic clinical trials.

Trial registration: ClinicalTrials.gov NCT00001289.

Show MeSH
Related in: MedlinePlus