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Striatal D₂ Receptor Availability After Shunting in Idiopathic Normal Pressure Hydrocephalus

¹ Department of Neurosurgery, Hamamatsu Medical Center, Hamamatsu, Japan; ² Positron Medical Center, Hamamatsu Medical Center, Hamamatsu, Japan; ³ Central Research Laboratory, Hamamatsu Photonics K.K., Hamamatsu, Japan; and ⁴ Department of Psychiatry, Hamamatsu University School of Medicine, Hamamatsu, Japan

Correspondence: For correspondence or reprints contact: Yasuomi Ouchi, MD, PhD, Human Imaging Research Laboratory, Molecular Imaging Frontier Research Center, Hamamatsu University School of Medicine, 1-20-1 Handayama, Higashi-ku, Hamamatsu 431-3192, Japan. E-mail: ouchi{at}pmc.hmedc.or.jp

Gait disturbance in idiopathic normal pressure hydrocephalus (iNPH) is reminiscent of parkinsonism. Our recent PET study showed reduction in postsynaptic D₂ receptor binding concomitant with a normality of presynaptic dopamine transporter binding. Here, we investigated the plasticity of D₂ receptor in treating iNPH patients with ventriculoperitoneal (VP) shunting using PET with ¹¹C-raclopride and discuss the contribution of D₂ receptor to the pathophysiology of iNPH. Methods: Eight iNPH patients participated in this study. After evaluation of their neuropsychologic abilities, all patients underwent 3-dimensional MRI and quantitative PET measurements twice before and 1 mo after VP shunting. MRI-based morphometric analyses were performed to examine postoperative variations of the ventricles. Estimation of binding potential (BP) for ¹¹C-raclopride was based on Logan plot analysis. Region-of-interest analysis was used to examine changes in ¹¹C-raclopride BP in the striatum. A 2-tailed paired t test was used for evaluating changes in PET and MRI parameters between conditions, and correlation analysis was used to investigate clinicopathophysiologic relevance (clinical vs. in vivo findings). Results: Clinical evaluation revealed significant recovery in a 5-m back-and-forth navigation test and an affect test and a mild increase in Mini-Mental State Examination scores after VP shunting. Significant postoperative increases in ¹¹C-raclopride BP were found in the nucleus accumbens and dorsal putamen, and the increases were significantly associated with emotional (Spearman rank r = 0.66, P < 0.05) and navigational improvement (r = 0.72, P < 0.05), respectively. The ¹¹C-raclopride BP increase in the striaum as a whole correlated significantly with improvement in general cognitive ability. There was a mild ventricular shrinkage after surgery, albeit there was no correlation of its size with clinical and PET parameters. Conclusion: Striatal upregulation of D₂ receptor after VP shunting is associated with amelioration of hypokinetic gait disturbance and anhedonic mentation in iNPH patients, indicating that the effect of VP shunting may reside in noninhibition of functionally suppressed D₂ receptor in the striatum. D₂ receptor responsiveness may indicate a mechanism for iNPH pathophysiology.

Key Words: idiopathic normal pressure hydrocephalus • D₂ receptor • raclopride • ventriculoperitoneal shunting • PET

COPYRIGHT © 2007 by the Society of Nuclear Medicine, Inc.

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