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Eye movement impairments in Parkinson's disease: possible role of extradopaminergic mechanisms.

Pinkhardt EH, Jürgens R, Lulé D, Heimrath J, Ludolph AC, Becker W, Kassubek J - BMC Neurol (2012)

Bottom Line: Patients exhibited the well known deficits such as increased saccade latency, reduced SPEM gain, and reduced frequency and amplitude of AVGS.Of the observed deficiencies, DBS-STN slightly improved AVGS frequency but neither AVGS amplitude nor SPEM or RS performance.We conclude that the impairment of SPEM in PD results from a cortical, conceivably non-dopaminergic dysfunction, whereas patients' difficulty to rapidly execute AVGS might be related to their BG dysfunction.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Neurology, University of Ulm, Oberer Eselsberg 45, 89081 Ulm, Germany. elmar.pinkhardt@uni-ulm.de

ABSTRACT

Background: The basal ganglia (BG) are thought to play an important role in the control of eye movements. Accordingly, the broad variety of subtle oculomotor alterations that has been described in Parkinson's disease (PD) are generally attributed to the dysfunction of the BG dopaminergic system. However, the present study suggest that dopamine substitution is much less effective in improving oculomotor performance than it is in restoring skeletomotor abilities.

Methods: We investigated reactive, visually guided saccades (RS), smooth pursuit eye movements (SPEM), and rapidly left-right alternating voluntary gaze shifts (AVGS) by video-oculography in 34 PD patients receiving oral dopaminergic medication (PD-DA), 14 patients with deep brain stimulation of the nucleus subthalamicus (DBS-STN), and 23 control subjects (CTL);In addition, we performed a thorough review of recent literature according therapeuthic effects on oculomotor performance in PD by switching deep brain stimulation off and on in the PD-DBS patients, we achieved swift changes between their therapeutic states without the delays of dopamine withdrawal. In addition, participants underwent neuropsychological testing.

Results: Patients exhibited the well known deficits such as increased saccade latency, reduced SPEM gain, and reduced frequency and amplitude of AVGS. Across patients none of the investigated oculomotor parameters correlated with UPDRS III whereas there was a negative correlation between SPEM gain and susceptibility to interference (Stroop score). Of the observed deficiencies, DBS-STN slightly improved AVGS frequency but neither AVGS amplitude nor SPEM or RS performance.

Conclusions: We conclude that the impairment of SPEM in PD results from a cortical, conceivably non-dopaminergic dysfunction, whereas patients' difficulty to rapidly execute AVGS might be related to their BG dysfunction.

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Related in: MedlinePlus

Oculomotor performance as a function of age. Blue filled circles, control subjects (CTL); green diamonds, patients with only dopamine therapy (PD-DA) or with additional STN-DBS (PD-DBS-on, green diamonds framed by black squares); red triangles, DBS patients during stimulation off (PD-DBS-off). a, latency of reactive saccades; arrows link "on"- and "off"-data of those 4 Patients who exhibited latencies outside the CTL-range during "off" (range accidentally delimited by latency-on-age regression of PD-DA + DBS-on, green line); solid black arrows mark near significant changes (p < 0.059); dotted arrows, non-significant changes. b, c, gain of horizontal (b) and upward (c) smooth pursuit of a sinusoidally moving target (0.375 Hz, horizontal ± 20°, vertical ± 15°).
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Figure 2: Oculomotor performance as a function of age. Blue filled circles, control subjects (CTL); green diamonds, patients with only dopamine therapy (PD-DA) or with additional STN-DBS (PD-DBS-on, green diamonds framed by black squares); red triangles, DBS patients during stimulation off (PD-DBS-off). a, latency of reactive saccades; arrows link "on"- and "off"-data of those 4 Patients who exhibited latencies outside the CTL-range during "off" (range accidentally delimited by latency-on-age regression of PD-DA + DBS-on, green line); solid black arrows mark near significant changes (p < 0.059); dotted arrows, non-significant changes. b, c, gain of horizontal (b) and upward (c) smooth pursuit of a sinusoidally moving target (0.375 Hz, horizontal ± 20°, vertical ± 15°).

Mentions: To detect possible correlations between patients' oculomotor results, neuropsychological performance, demographic data and clinical scores, we pooled the data of groups PD-DA and PD-DBS-on as their oculomotor and neuropsychological variables were statistically indistinguishable (except for GDS). UPDRS part III correlated with none of the parameters and scores considered; also a comparison of the subscore for rapid alternating hand movements with the frequency (N30) and gain (G(N30)) of rapidly alternating gaze shifts (AVGS) revealed no correlation. Likewisedisease duration (except for a significant correlation with FWT3-2, cf. below) was uncorrelated to any of the parameters considered.. Also, no correlation existed in the DBS subgroup between the changes of UPDRS III and of its alternating hand movements subscore resulting from STN-DBS and the concomitant changes of eye movement parameters. FWT3-2 correlated negatively with low frequency (0.125 Hz) horizontal (r = -0.46, p = 0.025) and downward (r = -0.46, p = 0.028) SPEM gain and positively with disease duration (r = 0.51, p = 0.014), while PANDA correlated only with 0.125 Hz downward SPEM gain (r = 0.48, p = 0.017). Otherwise, age was an important factor in both PD and CTL; high frequency (0.375 Hz) SPEM gain decreased with age in PD (r < -0.34, p < 0.02 for horizontal and downward, trend for upward; Figure 2b, c) as did N30 (r = -0.40 p = 0.011), whereas RS latency increased with age (r = 0.36, p = 0.012; Figure 2a). Qualitatively similar trends held for the CTL group (significant for downward SPEM, r = -0.42 p = 0.046) and latency r = 0.57, p = 0.002). In the case of saccade latency, the regression lines of latency on age had virtually identical slopes in PD and CTL, with the former being shifted upward by about 60 ms (Figure 1a).


Eye movement impairments in Parkinson's disease: possible role of extradopaminergic mechanisms.

Pinkhardt EH, Jürgens R, Lulé D, Heimrath J, Ludolph AC, Becker W, Kassubek J - BMC Neurol (2012)

Oculomotor performance as a function of age. Blue filled circles, control subjects (CTL); green diamonds, patients with only dopamine therapy (PD-DA) or with additional STN-DBS (PD-DBS-on, green diamonds framed by black squares); red triangles, DBS patients during stimulation off (PD-DBS-off). a, latency of reactive saccades; arrows link "on"- and "off"-data of those 4 Patients who exhibited latencies outside the CTL-range during "off" (range accidentally delimited by latency-on-age regression of PD-DA + DBS-on, green line); solid black arrows mark near significant changes (p < 0.059); dotted arrows, non-significant changes. b, c, gain of horizontal (b) and upward (c) smooth pursuit of a sinusoidally moving target (0.375 Hz, horizontal ± 20°, vertical ± 15°).
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3306761&req=5

Figure 2: Oculomotor performance as a function of age. Blue filled circles, control subjects (CTL); green diamonds, patients with only dopamine therapy (PD-DA) or with additional STN-DBS (PD-DBS-on, green diamonds framed by black squares); red triangles, DBS patients during stimulation off (PD-DBS-off). a, latency of reactive saccades; arrows link "on"- and "off"-data of those 4 Patients who exhibited latencies outside the CTL-range during "off" (range accidentally delimited by latency-on-age regression of PD-DA + DBS-on, green line); solid black arrows mark near significant changes (p < 0.059); dotted arrows, non-significant changes. b, c, gain of horizontal (b) and upward (c) smooth pursuit of a sinusoidally moving target (0.375 Hz, horizontal ± 20°, vertical ± 15°).
Mentions: To detect possible correlations between patients' oculomotor results, neuropsychological performance, demographic data and clinical scores, we pooled the data of groups PD-DA and PD-DBS-on as their oculomotor and neuropsychological variables were statistically indistinguishable (except for GDS). UPDRS part III correlated with none of the parameters and scores considered; also a comparison of the subscore for rapid alternating hand movements with the frequency (N30) and gain (G(N30)) of rapidly alternating gaze shifts (AVGS) revealed no correlation. Likewisedisease duration (except for a significant correlation with FWT3-2, cf. below) was uncorrelated to any of the parameters considered.. Also, no correlation existed in the DBS subgroup between the changes of UPDRS III and of its alternating hand movements subscore resulting from STN-DBS and the concomitant changes of eye movement parameters. FWT3-2 correlated negatively with low frequency (0.125 Hz) horizontal (r = -0.46, p = 0.025) and downward (r = -0.46, p = 0.028) SPEM gain and positively with disease duration (r = 0.51, p = 0.014), while PANDA correlated only with 0.125 Hz downward SPEM gain (r = 0.48, p = 0.017). Otherwise, age was an important factor in both PD and CTL; high frequency (0.375 Hz) SPEM gain decreased with age in PD (r < -0.34, p < 0.02 for horizontal and downward, trend for upward; Figure 2b, c) as did N30 (r = -0.40 p = 0.011), whereas RS latency increased with age (r = 0.36, p = 0.012; Figure 2a). Qualitatively similar trends held for the CTL group (significant for downward SPEM, r = -0.42 p = 0.046) and latency r = 0.57, p = 0.002). In the case of saccade latency, the regression lines of latency on age had virtually identical slopes in PD and CTL, with the former being shifted upward by about 60 ms (Figure 1a).

Bottom Line: Patients exhibited the well known deficits such as increased saccade latency, reduced SPEM gain, and reduced frequency and amplitude of AVGS.Of the observed deficiencies, DBS-STN slightly improved AVGS frequency but neither AVGS amplitude nor SPEM or RS performance.We conclude that the impairment of SPEM in PD results from a cortical, conceivably non-dopaminergic dysfunction, whereas patients' difficulty to rapidly execute AVGS might be related to their BG dysfunction.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Neurology, University of Ulm, Oberer Eselsberg 45, 89081 Ulm, Germany. elmar.pinkhardt@uni-ulm.de

ABSTRACT

Background: The basal ganglia (BG) are thought to play an important role in the control of eye movements. Accordingly, the broad variety of subtle oculomotor alterations that has been described in Parkinson's disease (PD) are generally attributed to the dysfunction of the BG dopaminergic system. However, the present study suggest that dopamine substitution is much less effective in improving oculomotor performance than it is in restoring skeletomotor abilities.

Methods: We investigated reactive, visually guided saccades (RS), smooth pursuit eye movements (SPEM), and rapidly left-right alternating voluntary gaze shifts (AVGS) by video-oculography in 34 PD patients receiving oral dopaminergic medication (PD-DA), 14 patients with deep brain stimulation of the nucleus subthalamicus (DBS-STN), and 23 control subjects (CTL);In addition, we performed a thorough review of recent literature according therapeuthic effects on oculomotor performance in PD by switching deep brain stimulation off and on in the PD-DBS patients, we achieved swift changes between their therapeutic states without the delays of dopamine withdrawal. In addition, participants underwent neuropsychological testing.

Results: Patients exhibited the well known deficits such as increased saccade latency, reduced SPEM gain, and reduced frequency and amplitude of AVGS. Across patients none of the investigated oculomotor parameters correlated with UPDRS III whereas there was a negative correlation between SPEM gain and susceptibility to interference (Stroop score). Of the observed deficiencies, DBS-STN slightly improved AVGS frequency but neither AVGS amplitude nor SPEM or RS performance.

Conclusions: We conclude that the impairment of SPEM in PD results from a cortical, conceivably non-dopaminergic dysfunction, whereas patients' difficulty to rapidly execute AVGS might be related to their BG dysfunction.

Show MeSH
Related in: MedlinePlus