Clinical studyUnilateral pallidotomy for Parkinson’s disease disrupts ocular fixation
Introduction
The resurgence of pallidotomy in the management of Parkinson’s disease (PD) is, in part, the result of a better understanding of the functional neuroanatomy of the basal ganglia. Recent models of the basal ganglia circuits involved in motor function include projections from different cortical motor regions which converge and pass in turn through the putamen, the globus pallidus interna (GPi) or substantia nigra pars reticulata (SNr), the thalamus and back to the motor cortex.1 Degeneration of dopaminergic nigrostriatal neurones in PD is thought to disrupt the normal striatal inputs to the GPi, resulting in excessive pallidal inhibition of the thalamus and consequently the motor cortex, leading to some of the abnormalities of movement which characterise the disease. Pallidotomy is generally thought to release the thalamocortical pathways from excessive inhibitory pallidal influence.2
Distinct cortico-cortical neuronal loop pathways mediating cognitive, behavioural and oculomotor functions passing through the basal ganglia parallel to the motor circuit have also been postulated.1 Although the motor deficits are more characteristic, abnormalities within these domains have also been described in patients with PD.3 Discrete lesions targeted in the GPi provide an opportunity to study its role in processes other than those mediated by the motor loop. Although neuropsychological sequelae of pallidotomy have been reported,[4], [5], [6], [7], [8], [9], [10], [11], [12], [13] the effect on oculomotor function has not been well studied. Averbuch-Heller et al. recently reported three patients with PD who developed square wave jerks (SWJs) following unilateral pallidotomy14 although their study was uncontrolled and there were potentially confounding effects of changes in dopaminergic medication.15 In another uncontrolled study modest impairment in internally mediated saccades without changes in visually guided saccades were reported in medicated patients with PD after unilateral pallidotomy, however fixation was not investigated.16 To investigate further the effect of pallidotomy on oculomotor function, we studied aspects of voluntary and visually guided horizontal saccades in five patients with advanced PD after overnight withdrawal of medication before and again 1 month after unilateral posteroventral pallidotomy. We assessed ocular fixation directly and also indirectly using a “gap” paradigm in which saccadic latency is reduced by the release of the inhibitory effects of fixation on saccade generation.17
Section snippets
Subjects
Five right-handed subjects fulfilling standard criteria for idiopathic PD18 were studied. All had disabling symptoms and motor fluctuations despite optimal pharmacotherapy. All patients showed significant impairment on volitional saccades tasks on our standard ocular motor testing battery.19 Specifically, they could not perform remembered saccade or anti-saccade tasks in accordance with the test instructions or gave saccade data that could not be analysed. This impairment was evident both
Results
Postoperative MRI performed within 3 days of surgery confirmed lesion placement in the GPi in all patients without evidence of haemorrhage along the electrode trajectory. There were no visual field defects postoperatively. Clinical results are shown in Table 1. The group mean percentage improvement in the “off” state at 1 month was 15% for UPDRS motor score, 26% for contralateral hand-tapping time, 37% for UPDRS Activities of Daily Living (ADL) and 28% for “on” state dyskinesia score.
For the
Discussion
The speed and accuracy of performance on the three visually guided saccade tasks as well as the fixation task were normal in the advanced PD group before pallidotomy. Qualitatively similar patterns of normal performance have been reported previously in PD.[24], [25], [26] Thus even moderately severe nigrostriatal dopamine deficiency does not seem to affect the neural pathways underlying the preparation of horizontal visually guided (including gap and predictive) saccades.
Although
References (40)
- et al.
Impaired frontostriatal cognitive functioning following posteroventral pallidotomy in advanced Parkinson’s disease
Brain Cogn.
(2000) - et al.
Parallel organization of functionally segregated circuits linking basal ganglia and cortex
Annu. Rev. Neurosci.
(1986) - et al.
Pallidotomy in Parkinson’s disease increases supplementary motor area and prefrontal activation during performance of volitional movements an H2(15)O PET study
Brain
(1997) - et al.
Behaviour and the basal ganglia
Adv. Neurol.
(1995) - et al.
Left posteroventral pallidotomy results in a deficit in verbal memory
Behav. Neurol.
(1998) - et al.
Motor, cognitive and behavioral performance following unilateral ventroposterior pallidotomy for Parkinson’s disease
Arch. Neurol.
(1998) - et al.
Cognitive functioning after pallidotomy for refractory Parkinson’s disease
J. Neurol. Neurosurg. Psychiatry
(1998) - et al.
Neurocognitive and psychosocial correlates of ventroposterolateral pallidotomy surgery in Parkinson’s disease
Neurosurg. Focus
(1997) - et al.
Neuropsychological, neurological and functional outcome following pallidotomy for Parkinson’s disease. A consecutive series of eight simultaneous bilateral and twelve unilateral procedures
Brain
(1998) - et al.
Cognitive sequelae of unilateral posteroventral pallidotomy
Arch. Neurol.
(1997)
Neuropsychological consequences of posteroventral pallidotomy for the treatment of Parkinson’s disease
Neurology
Neuropsychological outcome following unilateral pallidotomy
Brain
Square-wave jerks induced by pallidotomy in parkinsonian patients
Neurology
Catecholamine depletion produces irrepressible saccades in normal individuals
Ann. Neurol.
Eye movements in Parkinson’s disease: before and after pallidotomy
Invest. Ophthalmol. Vis. Sci.
Comparison of the discharge characteristics of the omnipause neurones and superior colliculus fixation neurones in the monkey: implications for control of fixation and saccade behaviour
J. Neurophysiol.
The relevance of the Lewy body to the pathogenesis of idiopathic Parkinson’s disease
J. Neurol. Neurosurg. Psychiatry
The effects of age and mood on saccadic function in older individuals
J. Gerontol. B Psychol. Sci. Soc. Sci.
The effect of unilateral posteroventral pallidotomy on the kinematics of the reach to grasp movement
J. Neurol. Neurosurg. Psychiatry
Cited by (22)
“Zickzackbewegungen”: A Back-to-Basics Review of Square Wave Jerks
2023, Advances in Ophthalmology and OptometryOcular and visual disorders in Parkinson's disease: Common but frequently overlooked
2017, Parkinsonism and Related DisordersExperimental support that ocular tremor in Parkinson's disease does not originate from head movement
2014, Parkinsonism and Related DisordersCitation Excerpt :The authors found no correlation between the ocular and appendicular tremor and concluded that the ocular tremor represented primary eye oscillations [1]. Although also apparent in published figures in a number of other studies [2–4], all of which utilized some form of head restraint, ocular tremor had otherwise been a largely unrecognized feature of PD. Utilizing comparatively more modern and sensitive eye tracking equipment, we consistently observed binocular tremor in 112 subjects with PD and in 2 of 60 asymptomatic control subjects, both who converted to clinical PD within 3 years of their initial evaluations [5].
New perspectives on the pathophysiology of Parkinson's disease as assessed by saccade performance: A clinical review
2013, Clinical NeurophysiologyCitation Excerpt :Blekher et al. (2000) showed that pallidotomy decreases the peak saccadic velocity of internally mediated saccades. Similarly, O’Sullivan et al. (2003) showed that pallidotomy disrupts ocular fixation, although there was no difference in saccadic latency or accuracy, the number of saccadic anticipations, or the ability to generate predictive saccades. Meanwhile, pallidal DBS improved latency of reflexive saccades and delayed latency of voluntary saccades in Huntington’s disease, and also reduced patient’s ability to suppress unwanted saccades decreased with stimulation, disrupting fixation (Fawcett et al., 2005).
Disorders of higher gaze control
2011, Handbook of Clinical NeurologyCitation Excerpt :Depending on the location of the electrode fixation, instability may occur (Wark et al., 2008). A disruption of ocular fixation has also been reported after a unilateral pallidotomy (O'Sullivan et al., 2003). Abnormalities in smooth pursuit in Parkinson's disease are recognized (Shibasaki et al., 1979; Teravainen and Calne, 1980; White et al., 1983; Gibson and Kennard, 1987; Gibson et al., 1987; Sharpe et al., 1987; Rascol et al., 1989a; Pinkhardt et al., 2009), particularly in smooth pursuit gain (White et al., 1983; Rascol et al., 1989a), but have been less well explored.
Nystagmus and saccadic intrusions
2011, Handbook of Clinical NeurologyCitation Excerpt :They can be almost continuous in these diseases, thereby producing square-wave oscillations (Abel et al., 1984). They can sometimes develop following pallidotomy in parkinsonian patients (Averbuch-Heller et al., 1999b; O'Sullivan et al., 2003). Macrosquare-wave jerks consist of large (usually > 5°) oscillations occurring at a frequency of 2–3 Hz.