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Subthalamic nucleus stimulation modulates audiospinal reactions in Parkinson disease

From the Department of Neurology, Christian-Albrechts-University, Kiel, Germany.

Address correspondence and reprint requests to Prof. Dr. J. Volkmann, Dept. of Neurology, Christian-Albrechts-University, Schittenhelmstr. 10 m D-24105 Kiel, Germany

Background: Axial symptoms of Parkinson disease (PD) may result from dysfunctional basal ganglia–brainstem connections. In this study, we assessed whether modulation of basal ganglia activity by high-frequency stimulation of the subthalamic nucleus (STN-HFS) in PD had an impact on the brainstem-controlled startle system.

Methods: We assessed auditory startle responses (recorded from right orbicularis oculi, masseter, sternocleidomastoid, biceps brachii, and soleus muscle) and audiospinal facilitation (startle conditioned soleus H-reflexes at interstimulus intervals of 0–250 msec) in 24 patients with PD with chronically implanted, bilateral STN electrodes in the stimulation on (STIM ON) and off condition (STIM OFF) and 20 healthy controls.

Results: The mixed linear analysis of variance model revealed a significant effect for the startle onset latency in the orbicularis oculi muscle for the factors GROUP (patients with PD vs controls; p < 0.0001, F = 44.66) and STIM (nested within GROUP) (p = 0.0034, F = 8.79). Audiospinal facilitation was modulated by STN-HFS as shown by highly significant effects for STIM [GROUP] (p < 0.0001, F = 15.9), ISI [GROUP] (p < 0.0001, F = 3.5), and the interaction of ISI x STIM [GROUP] (p = 0.0085, F = 2.65) in the mixed linear model.

Conclusion: High-frequency stimulation of the subthalamic nucleus alters the excitability of the brainstem startle system in Parkinson disease, most likely by releasing the reticular motor system from abnormal descending input of the basal ganglia via pallidotegmental pathways.

GLOSSARY: ANOVA = analysis of variance; AUC = area under the curve; ISI = interstimulus intervals; LEDD = levodopa equivalent daily dosage; NRGC = nucleus reticularis gigantocellularis; NRPC = nucleus reticularis pontis caudalis; PD = Parkinson disease; PPN = pedunculopontine nucleus; STN-HFS = high-frequency stimulation of the subthalamic nucleus; UPDRS = Unified Parkinson's Disease Rating Scale.

j.volkmann{at}neurologie.uni-kiel.de

Supported by the Sonderforschungsbereich 654 (project A7) of the Deutsche Forschungsgemeinschaft and by a junior grant of the research commission of Christian-Albrechts-University to Dr. Pötter.

Disclosure: The authors report no conflicts of interest.

Received December 10, 2006. Accepted in final form October 22, 2007.