The neurophysiology and effect of deep brain stimulation in a patient with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine–induced parkinsonism

Case report

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Parkinsonism caused by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) exposure was first identified in intravenous drug users. This neurotoxicant has since been used extensively in nonhuman primates to induce an experimental model of Parkinson disease (PD). In this study, the authors examined the intraoperative physiological characteristics and efficacy of subthalamic nucleus deep brain stimulation (DBS) in 1 of only 4 known living patients with MPTP-induced parkinsonism. The physiological recordings were consistent with recordings from MPTP-treated primates and humans with PD, thus providing further validation for the MPTP model in the study of the neurophysiology of the nigrostriatal dopaminergic deficit in PD. Furthermore, DBS produced a significant clinical improvement in this patient similar to the improvement seen after DBS in patients with idiopathic PD. This unique case has important implications for translational research that employs the MPTP-primate model for symptomatic therapy in PD.

Abbreviations used in this paper: DBS = deep brain stimulation; MPTP = 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine; PD = Parkinson disease; STN = subthalamic nucleus; UPDRS III = Unified Parkinson Disease Rating Scale, Part III.

Article Information

Address correspondence to: Chadwick W. Christine, M.D., Department of Neurology, School of Medicine, University of California San Francisco, 400 Parnassus Avenue, Room A838, San Francisco, California 94143. email: chad.christine@ucsf.edu.

© AANS, except where prohibited by US copyright law.

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Figures

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    Characteristic oscillatory activity recording from an STN neuron. A: Segment of the raw signal recorded from a well-isolated neuron. B: Autocorrelogram for the same spike train illustrating rhythmic peaks in firing probability ~ 50 msec apart. C: Frequency spectrum for the spike train (normalized to the mean of 100 spectra from shuffled interspike intervals). Horizontal dotted line is the threshold for significance (p < 0.01), adjusted for multiple comparisons, based on the mean and standard deviation in normalized spectrum between 300–500 Hz.

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    Postoperative axial T2-weighted MR image in the plane of the dorsal STN (4-mm inferior to the intercommissural line). The leads are seen as signal voids lateral to the anterior border of the red nucleus.

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