Pedunculopontine nucleus stimulation induces monocular oscillopsia

Université Joseph Fourier, Grenoble, France and INSERM U836, Grenoble Institut des Neurosciences, Grenoble, France.
Journal of neurology, neurosurgery, and psychiatry (Impact Factor: 6.81). 03/2009; 80(2):228-31. DOI: 10.1136/jnnp.2008.146472
Source: PubMed


Two patients with Parkinson's disease with pedunculopontine nucleus (PPN) stimulation for gait impairments reported "trembling vision" during the setting of the electrical parameters, although there was no clinically observable abnormal eye movement. Oculomotor recordings revealed frequency locked voltage dependent vertical or oblique movements of the eye ipsilateral to the active contact, suggesting current spreading to the mesencephalic oculomotor fibres. These results emphasise the difficulty of stimulating this mesencephalic region.

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    • "PPNa stimulation induced adverse effects at relatively low voltages, including oscillopsia and limb myoclonus at low frequency and paraesthesia at higher frequencies. The oculomotor effects are likely to result from the recruitment of the most lateral and caudal fibres of the oculomotor nerve (Ferraye et al., 2009). "
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    ABSTRACT: Gait disturbances are frequent and disabling in advanced Parkinson's disease. These symptoms respond poorly to usual medical and surgical treatments but were reported to be improved by stimulation of the pedunculopontine nucleus. We studied the effects of stimulating the pedunculopontine nucleus area in six patients with severe freezing of gait, unresponsive to levodopa and subthalamic nucleus stimulation. Electrodes were implanted bilaterally in the pedunculopontine nucleus area. Electrode placement was checked by postoperative magnetic resonance imaging. The primary outcome measures were a composite gait score, freezing of gait questionnaire score and duration of freezing episodes occurring during a walking protocol at baseline and one-year follow-up. A double-blind cross-over study was carried out from months 4 to 6 after surgery with or without pedunculopontine nucleus area stimulation. At one-year follow-up, the duration of freezing episodes under off-drug condition improved, as well as falls related to freezing. The other primary outcome measures did not significantly change, nor did the results during the double-blind evaluation. Individual results showed major improvement of all gait measures in one patient, moderate improvement of some tests in four patients and global worsening in one patient. Stimulation frequency ranged between 15 and 25 Hz. Oscillopsia and limb myoclonus could hinder voltage increase. No serious adverse events occurred. Although freezing of gait can be improved by low-frequency electrical stimulation of the pedunculopontine nucleus area in some patients with Parkinson's disease our overall results are disappointing compared to the high levels of expectation raised by previous open label studies. Further controlled studies are needed to determine whether optimization of patient selection, targeting and setting of stimulation parameters might improve the outcome to a point that could transform this experimental approach to a treatment with a reasonable risk-benefit ratio.
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    ABSTRACT: Postural instability and falls are a major source of disability in patients with advanced Parkinson's disease. These problems are currently not well addressed by either pharmacotherapy nor by subthalamic nucleus deep-brain stimulation surgery. The neuroanatomical substrates of posture and gait are poorly understood but a number of important observations suggest a major role for the pedunculopontine nucleus and adjacent areas in the brainstem. We conducted a double-blinded evaluation of unilateral pedunculopontine nucleus deep-brain stimulation in a pilot study in six advanced Parkinson's disease patients with significant gait and postural abnormalities. There was no significant difference in the double-blinded on versus off stimulation Unified Parkinson's Disease Rating Scale motor scores after 3 or 12 months of continuous stimulation and no improvements in the Unified Parkinson's Disease Rating Scale part III scores compared to baseline. In contrast, patients reported a significant reduction in falls in the on and off medication states both at 3 and 12 months after pedunculopontine nucleus deep-brain stimulation as captured in the Unified Parkinson's Disease Rating Scale part II scores. Our results suggest that pedunculopontine nucleus deep-brain stimulation may be effective in preventing falls in patients with advanced Parkinson's disease but that further evaluation of this procedure is required.
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    ABSTRACT: This article reviews topics of interest to the ophthalmologist relating to the most common neurologic protein misfolding disorders. Many neurodegenerative diseases are pathologically associated with misfolded proteins. These diseases cause a profound impact of disability to the individual and society. Alzheimer's disease costs alone are estimated to be over US$225 billion annually in the USA. The ophthalmologist is often asked to provide an opinion regarding the cause of visual symptoms in patients with these unique disorders. The categorization of neurodegenerative diseases has evolved based on advances in genetic, molecular and pathological research. In many neurodegenerative diseases, aggregation of a misfolded protein is responsible for the development of pathologic inclusions. When the misfolded protein is tau or synuclein, these diseases are called tauopathies or synucleinopathies, respectively. This article focuses on ophthalmic findings in some of the most common tauopathies and synucleinopathies: Alzheimer's disease, progressive supranuclear palsy, Parkinson's disease, dementia with Lewy bodies and multisystem atrophy.
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